There are currently no reliable predictive factors for gastric cancer recurrence. The aim of this study was to evaluate the relationship between bcl-2 expression and risk of gastric cancer recurrence.From January 1996 to December 2007, 449 gastric cancer patients who underwent curative resection were retrospectively studied. The expression levels of bcl-2 were examined by immunohistochemistry. Logistic regression was performed to identify independent risk factors for overall recurrence of gastric cancer.151 patients (33.6%) experienced recurrences. The median time to recurrence was 17.0 months, 113 (74.8%) patients had recurrences within 2 years. Peritoneal recurrence was the most prevalent pattern, followed by hematogenous metastasis in which the liver was the most common site. Depth of invasion, lymph node metastases, and negative expression of bcl-2 were independent risk factors for overall recurrence. The overall survival time of recurrent patients was 22.7 months. The median survival time after recurrence was 6.7 months.The depth of invasion, lymph node metastases and expression of bcl-2 are independent factors for predicting gastric cancer recurrence. Although the incidence of gastric cancer has been declining substantially for several decades, it is still the fourth most common cancer and the second most frequent cause of cancer death ,2. AlthoTNM Staging Classification for Carcinoma of the Stomach  [Between January 1996 and December 2007, 4,426 patients with histologically confirmed primary gastric adenocarcinoma underwent gastrectomy at the Department of Gastric Cancer and Soft Tissue Sarcoma in Fudan University Shanghai Cancer Center. Out of these patients, 449 cases were selected. These patients’ specimens were stained immunohistochemically. Data were retrieved from patients’ operative and pathological reports. Follow-up data were obtained by phone, letter, and the outpatient clinical database. Staging was performed according to the Union for International Cancer Control (UICC) n, 2010) . A follo2O2 and blocked with non-specific staining blocking reagent. After overnight incubation at 4°C with anti-bcl-2 antibody (diluted 1:100), sections were treated according to standard immunoperoxidase methods. Negative control sections were subjected to the same procedure, except that the first antibody was replaced by PBS. No positive staining was observed in the controls. The location of staining for bcl-2 was predominantly in cytoplasm and cytomembrane.Bcl-2 was detected by the immunohistochemical method. Antibodies were purchased from Dako . Immunohistochemical staining was performed by the enhanced labeled polymer system method. Paraffin sections were deparaffinised with xylene and hydrated with ethanol/deionized water. Sections were then incubated with methanol/0.3% HAll slices were independently evaluated by two pathologists. The percentage of immunoreactive cells and staining intensities were evaluated. The percentage of immunoreactive cells was graded on a scale of 0 to 4: no staining was scored as 0, 1 to 10% of cells stained scored as 1, 11 to 50% as 2, 51 to 80% as 3, and 81 to 100% as 4. The staining intensities were graded from 0 to 3: 0 was defined as negative, 1 as weak, 2 as moderate, and 3 as strong, respectively. The raw data were converted to an immunohistochemical score (IHS) by multiplying the quantity and intensity scores. An IHS score of 9 to 12 was considered as strong immunoreactivity (+++), 5 to 8 as moderate (++), 1 to 4 as weak (+), and 0 as negative (-). Cases with a score of less than 1 were considered as negative, and those with ≥1 were regarded as positive [t-test or Pearson chi-square test as appropriate. Factors that were deemed of potential importance on univariate analysis were included in the multivariate analysis. Logistic regression was used to estimate related factors for recurrence. The accepted level of significance was P < 0.05. Statistical analyses and graphics were performed using the SPSS 13.0 statistical package .Data were presented as the mean ± SD or the median for numeric parameters. The patients’ features and clinical characteristics were analyzed using the two-tailed Student The study included 307 male and 142 female patients (2.2:1) with a mean age of 57 years. There were 49 (10.9%) early gastric cancers and 400 (89.1%) advanced gastric cancers. According to histological type, well-differentiated tumors were observed in 7 (1.5%) patients, moderately-differentiated in 149 (33.2%) patients, and poorlydifferentiated tumors in the remaining 293 (65.3%) patients. According to Borrmann type, 49 (10.9%) were type 0, 32 (7.1%) type I, 14 (3.1%) type II, 333 (74.2%) type III, and 21 (4.7%) type IV. Of these patients, 147 (32.7%) had tumors located in the upper third of the stomach, 65 (14.5%) had tumors in the middle third, 212 (47.2%) had tumors in the lower third, and 25 (5.6%) had tumors occupying two-thirds or more of the stomach. Lymph node metastasis was observed in 326 patients, and the metastasis rate was 72.6%. The distribution of pathological stage was as follows: 35 (7.8%) patients belonged to stage IA, 34 (7.6%) IB, 50 (11.1%) IIA, 75 (16.7%) IIB, 82 (18.3%) IIIA, 80 (17.8%) IIIB, and 93 (20.7%) IIIC.Bcl-2 expression was positive in 21.2% of all gastric cancer tissues. Bcl-2 staining was observed in the cytoplasm and cytomembrane of carcinoma cells  patients during the follow-up period. The median time to recurrence was 17.0 months (range from 2.0 to 91.0 months), and the mean time was 21.1 months. Among patients with recurrence, 113 (74.8%) had recurrence within 2 years. The frequency and rate of recurrence are demonstrated in Figure Of the 151 patients with recurrence, 58 38.4%) were diagnosed with peritoneal recurrence, which was the most prevalent, 49 (32.5%) patients had hematogenous metastases, which was the second most common recurrence pattern, and liver was the most frequently involved organ; it was implicated in 57.1% of all recurrent patients. Other recurrences were loco-regional , distant lymph node metastases , or at multiple sites  , 7.3 months (2.4 to 11.7), 7.0 months (2.5 to 17.1), and 6.1 months (3.9 to 7.9), respectively. Patients with peritoneal and distant lymph node recurrence had a shorter survival time; however this was not statistically significant.The main findings of this study were that (1) peritoneal recurrence was the most prevalent recurrence pattern after curative surgery, and (2) the depth of invasion, lymph node metastases and negative expression of bcl-2 were independent risk factors for overall recurrence.Gastric cancer is one of the most common malignancies worldwide. Although the prognosis of patients with gastric cancer has improved as a result of better diagnostic techniques and therapeutic strategies, gastric cancer is still the second leading cause of cancer-related deaths . The diset al.[In our study, 151 (33.6%) patients had recurrence during the follow-up period. The mean time to recurrence was 21.1 months; 113 patients (74.8%) had recurrence within 2 years. This result shows that most gastric cancer recurrence occurs within 2 years, and is consistent with other studies -12. Yoo et al. reported [It has been reported that the most common recurrence patterns are hematogenous recurrence and peritoneal dissemination in gastric cancer ,12-14. Ireported  that thereported . This diet al.[et al.[et al.[Recurrence is frequent in gastric cancer patients after undergoing radical gastrectomy. Therefore, it is important to identify patients at a high risk of recurrence. In this study, univariate analysis showed that Borrmann type, depth of invasion, and lymph node status were associated with overall recurrence. Logistic regression demonstrated that depth of invasion and lymph node metastases were independent risk factors for overall recurrence. Consistent with our findings, previous studies have showed that traditional clinicopathological factors such as serosal exposure, histological type, depth of invasion, and lymph node metastasis were risk factors for recurrence -19. Howeet al. reportedl.[et al. showed tl.[et al. reportedIn conclusion, the present study demonstrated that peritoneal recurrence was the most common recurrence pattern after curative gastrectomy. Depth of invasion, lymph node metastases, and negative expression of bcl-2 predict greater risk of recurrence. These findings may provide some useful information for followup in gastric cancer patients who have undergone surgery for resection. Specifically, it is necessary to conduct an intensive follow-up plan for gastric cancer patients with negative expression of bcl-2. However, the small scale and the retrospective design were shortcomings of the current study. Further large-scale, prospective studies should be performed to validate the usefulness of bcl-2 in detecting tumor recurrence in patients with gastric cancer.The authors declare that they have no competing interests.JHW, XWL and YNW conceived and designed the experiments. JHW and XWL performed the experiments. JHW, XWL and HC analyzed the data. HC and YNW contributed reagents/materials/analysis tools. JHW and XWL wrote the paper. All authors read and approved the final manuscript.


Cardiac MRI (CMR) is increasingly being used clinically to assess the regional thickness of the compacted and trabeculated layers of the left ventricle (LV) in patients with suspected non-compaction. However, there is no consensus on whether the short or longitudinal axis view is preferred. We sought to assess the compacted and trabeculated layers in a young ventricular dysrhythmia population with age matched controls and to compare the measurements derived from both the short axis and longitudinal views.The study consisted of 91 patients aged 20 to 49 years with ventricular dysrhythmia (VT) and 23 age-matched normal subjects. Regional wall thickness was assessed in short axis CMR cine views using a basal, mid and apical slice as well as in longitudinal views using the 2, 3, and 4 chamber view. The images were analyzed at end-diastole where the compacted layer was measured following the standardized 16-segment model. The apical segments were chosen 2 cm from the most apical portion of the LV for both short and longitudinal views. Within each wall segment, the most prominent trabeculation was measured, and the ratio of the trabeculated to compacted layer was compared between the VT group and controls in both views.The mean age was 38 years and 48 (42%) were men. In the VT group, 31 had premature ventricular contractions and 60 had ventricular tachycardia. VT patients were associated with larger LV end-diastolic volumes , larger LV mass (58 g/m2 vs. 49.9 g/m2 p=0.001), and lower LV ejection fraction (50% vs. 60% p=0.015) as compared to the control group, respectively. Using the short axis view, the prevalence of trabeculated to compacted layer ratios ≥ 2.0, ≥ 2.1, ≥ 2.2 and ≥ 2.3 were 18.4%, 15.2%, 9.2% and 8.7% in the VT group, respectively while the prevalence in the control group was 13% for a ratio ≥ 2.0 with no segments ≥ 2.1. Using the same ratio cut points for the longitudinal view, the prevalence was 39.1%, 32.6%, 27.2% and 16.3% in the VT group and 43%, 39.1%, 21.7%, and 13% in controls, respectively.In this young cohort, the trabeculated to compacted ratio ≥ 2.1 is only present in patients with ventricular dysrhythmias and not seen in normal controls using short axis planes, suggesting that increased thickness of the trabeculated layer in young subjects may be associated with the risk of ventricular dysrhythmia. However, the ratio ≥ 2.3 is equally prevalent in both groups using longitudinal planes. Our findings suggest that the short axis view may be more discriminatory then the longitudinal view in identifying normal subjects. More importantly, there is a clear need to standardize the assessment of the trabeculated to compacted layer ratio in clinical practice.None


Cardiac MRI (CMR) is increasingly used to further investigate patients in whom amyloidosis is suspected on echocardiography. Late gadolinium enhancement (LGE) reflects expansion of the interstitium, and circumferential subendocardial LGE has been reported to be a typical finding in AL amyloidosis; by contrast, a more diffuse transmural LGE pattern has been associated with ATTR (transthyretin amyloidosis).We studied patients who had been referred to the UK National Amyloidosis Centre (NAC) between June 2007 and June 2011 with a possible diagnosis of cardiac amyloidosis based on the findings of CMR performed at their local centres. We analysed the CMR images and LGE patterns in the left ventricle at the base, mid wall and apex. The LGE pattern at each level was described as circumferential if it involved all segments at either the base, mid or apical levels, and transmural if it involved the subendocardium through to the epicardial layer.Studies were performed in 32 UK centres, and we were able to obtain 103 studies for analysis. The mean age of the patients was 69.2 ± 11.4 years with a male predominance (72.7%). Amyloidosis was confirmed at the NAC in 99 patients and excluded in 4 patients. The amyloid type was AL in 39 patients (39.4%), ATTR in 55 patients (55.5%) and rarer forms of non-AL, non-TTR amyloid in 5 patients (5.1%). We report the CMR findings in 94 patients with AL or ATTR. Interventricular wall thickness was greater in ATTR compared to AL . LGE was evident in all patients with ATTR amyloid and 36 patients (92.3%) with AL (p=0.07). Right ventricular (RV) LGE was also present in all patients with TTR amyloid and 26 patients (66.7%) with AL (p <0.01). A gradient with greater LGE at the base than the apex was more often present in ATTR (62.5% vs 35.9% in AL - p <0.01). Circumferential subendocardial LGE was present in only 8 patients (20.5%) with AL and only 2 patients (3.6%) with ATTR (p <0.01). Circumferential transmural LGE was present in 6 patients with ATTR (10.7%) and none with AL amyloid (p<0.01). Fifty-two patients with ATTR (92.9%) demonstrated transmural LGE in at least one segment compared to 12 patients (30.8%) with AL amyloid (p <0.01).This study of CMR performed in multiple regional centres confirms its high diagnostic value in cardiac amyloidosis. Whilst greater wall thickness and a transmural pattern of LGE was more suggestive of ATTR, only the absence of RV LGE in one-third of AL patients reliably distinguished the two types of amyloid.Funding for this study was obtained from the British Heart Foundation Clinical Research Training Fellowship no. FS/09/063/28026 to J.D.


In conclusion, the missense mutation R1268Q in the ABCC6 gene is not a specific marker of PXE, but is associated with the disease state of AS.Angioid streaks (AS) are hereditary eye conditions caused by breaks in the elastic layer of Bruch’s membrane. Patients with AS are also frequently affected with pseudoxanthoma elasticum (PXE). The locus of PXE has been reported to exist in chromosome 16p13.1, and the ABCC6 gene in this locus has been identified as the causal gene of PXE. In this study we investigated the association of the ABCC6 gene and AS. Elucidation of the causal gene of AS will be useful for gene diagnosis in the future. Many mutations in patients with PXE are found in exons 24 and 27 of the ABCC6 gene in previous reports. Therefore, we examined exons 24 and 27 of the ABCC6 gene using the single-strand conformation polymorphism technique. There was no mutation or polymorphism in exon 24. The base substitution of G3803A was identified in exon 27, with a change in the amino acid from CGG to CAG (R1268Q). The genotype frequencies in patients with AS were G/G 52% (23/44), G/A 32% (14/44) and A/A 16% (14/44). In control subjects, the genotype frequencies were G/G 69% (107/154), G/A 29% (44/154) and A/A 2% (3/154). Highly significant differences were observed in both genotype and allele frequencies of R1268Q between patients with AS and control subjects ( Angioid streaks (AS) OMIM 607140) are hereditary eye condition caused by breaks in the elastic layer of Bruch’s membrane. However the inheritance pattern for AS has not yet been clarified. Although visual acuity does not decrease due to the presence of angioid streaks themselves, visual loss does occur due to the secondary hemorrhage and/or exudation from choroidal neovascularization (CNV) that develops through the streaks in the macula. About 70% of patients with AS experience decrease in central visual acuity by the age of 50 40 are he. AS haveOn the other hand, PXE is a rare disease of the connective tissue and it exhibits an autosomal recessive OMIM 264800) or an autosomal dominant OMIM 177850) inheritance pattern. It is characterized by progressive calcification of elastic fibers in the skin, Bruch’s membrane of the eye, and the cardiovascular system. The association of AS with PXE was first reported by Groenblad  and 17 females (age range 19-71 years) aged between 19 and 78 years with a mean ± SD of 61.2 ± 9.7 years. Except for a 19 year-old female, all other patients were older than 48 years of age. Ophthalmological examinations including measurement of visual acuity, fundus examination, and fluorescein angiography (FA) were conducted in all patients. CNV associated with AS was diagnosed based on fundus examination and FA. Dermatological examination and/or skin biopsy were conducted for the diagnosis of PXE. While a diagnosis of positive PXE was made by macroscopic dermatological examination or skin biopsy, a diagnosis of negative PXE was always based on a skin biopsy. As a result, PXE was positive in 27 patients  and negative in 5 patients, while PXE status was unclear in the remaining 12 patients because they refused to undergo skin biopsy.As controls, we investigated 154 healthy unrelated Japanese subjects  aged between 50 and 81 years with a mean of 57.4 ± 6.4 years. All control subjects were healthy volunteers who visited the Comprehensive Health Evaluation Center of Nihon University School of Medicine for a routine medical checkup. They had no remarkable medical history including AS documented by fundus examinations. Their best-corrected vision was 20/20 or better.Informed consent was obtained from all subjects as per the protocol approved by the ethical committee of Nihon University. This investigation was performed according to the guidelines of the Declaration of Helsinki.2, 0.2 mM of each dNTP, and 0.5 units LA Taq polymerase (5 units/μl) . The thermoprofile was 94°C for 3 minutes, followed by 35 cycles of 98°C for 25 seconds, 63°C for 30 seconds, 72°C for 1 minute, and a final extension at 72°C for 10 minutes. Samples were heat denatured, and electrophoresed with two different 5% polyacrylamide gels, one with and one without 5% glycerol, using an automated LASER DNA Analyzer . Samples that exhibited an abnormal migration band for the SSCP method were reamplified, and sequenced directly after subcloning, using an automated DNA sequencer .Genomic DNA was extracted from whole blood according to standard procedures . Data of2, 0.2 mM of each dNTP, 5 units LA Taq polymerase , and 1 x LA Taq polymerase buffer. The thermoprofile was the same as for the SSCP procedure. The PCR products were digested with BstXI and electrophoresed on 1.5% agarose gels. These products were stained with ethidium bromide, and visualized under ultraviolet light. The G/G genotype exhibits a single band of 207 bp, the G/A genotype exhibits three bands of 207 bp and 134 bp, 73 bp, and the A/A genotype exhibits two bands of 134 bp and 73 bp.The restriction enzyme fragment length polymorphism (RFLP) method was used in genotyping. The PCR products for exon 27 were generated using the primers 5’-CTGAAGCTGATAGAGGTGGGCCATC-3’, and 5’-TTGAAGGACACGCCCTGCACAGCCA-3’. In a reaction mixture of 20 μl, polymerase chain reaction was performed using 200 ng human genomic DNA, 4 pmol of each PCR primer, 2.5 mM MgClP values less than 0.05 were considered to be significant differences.Data are presented as mean ± SD. All statistical analyses were done with StatView, ver. 5.0. The chi-square test was used in all statistical analyses. The SSCP analysis showed no abnormal migration band in exon 24 of the ABCC6 gene. In exon 27, abnormal migration bands were detected. After direct sequencing, base substitution of G3803A was identified in exon 27. This substitution yields an amino acid change from CGG (Arg) to CAG (Gln) (R1268Q)  (Table We investigated the frequencies of the G3803A R1268Q) genotypes by the RFLP method . A statistically significant difference in genotype frequency was observed between the patients with AS (n=44) and control subjects (n=154) (p<0.001) (Table p=0.16) (Table p<0.0002). A significant difference in frequency of allele A was also observed between patients with AS and control subjects (p<0.002).The genotype frequencies in the control subjects were G/G 69% (107/154), G/A 29% (44/154) and A/A 2% (3/154). These results are in agreement with the predicted Hardy-Weinberg equilibrium values , suggesting that there is no racial difference in the frequency of R1268Q.Germain et al  determinet al . There wet al . Significant differences in genotype and allele frequencies of R1268Q were observed between patients with AS and control subjects. However, no significant difference in allele frequency of R1268Q was found between patients with AS with and without PXE. These findings indicate that R1268Q is not a specific marker of PXE, but is a missense mutation associated with the disease state of AS. Abnormalities in the ABCC6 gene not only cause PXE but are also associated with the onset of AS.


Golgi protein 73 (GP73), which is up-regulated in hepatocellular carcinoma (HCC), has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV) infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease. Inconsiin vitro . On the in vitro . In addiin vitro ,12.Despite the large number of studies suggesting GP73 as a serum marker for HCC, at the present time, the absolute positive markers for HCC are still lacking, and even those characterized by high sensitivity and specificity (such as α-Fetoprotein (AFP), Glypican-3 (GPC3), Des-γ-Carboxy Prothrombin (DCP) and GP73, used alone or in combination) do not widely applied for clinical use. It is well known that the main established risk factors for HCC development are chronic viral hepatitis B and C infection. Liver cirrhosis may also lead to HCC development. HCV causes HCC probably via an indirect pathway by causing chronic inflammation and cirrhosis. Alcoholic liver disease and autoimmune liver disease are also associated with the development of HCC . Interes2.2.1.et al. reported that GP73 was present at high levels in HepG2.2.15 cells (a cell line that supports active HBV replication), but was absent in HepG2T14.1 cells (an HBV-transfected cell line that does not support HBV replication) and in HBV-free HepG2 cells [p < 0.05). Huh7, Huh7.5.1, Hep3B, 293T and HUVEC cells showed dramatically higher levels of GP73, approximately 300 to 900 folds than that in HepG2 cells. To identify the effects of HCV infection on GP73 expression, GP73 mRNA level was detected in Huh7 cells 24 h after HCV infection. The mRNA levels of GP73 in HCV infected Huh7 cells were slightly down regulated  plays a pivotal role in recruiting lympholeukocytes and macrophages to the liver . Therefo2.3.Significant increases of GP73 were previously found in liver disease due to viral causes  or nonviral causes , while the sera or liver tissue specimen were mainly from chronic liver disease. Therefore, to further observe the long-term effects of HCV infection on GP73 expression in hepatoma carcinoma cells, we detected the GP73 mRNA level in Huh7.5.1 cells at different time points after HCV infection. As shown in Similar results were also found in HepG2 cells. Marked CPE were shown in HepG2 cells transfected with more than 0.8 μg of HCV RNA , and GP7Increased levels of ALT were found in the supernatant of Huh7.5.1 cells at later days of HCV infection . However2.4.et al. found that GP73 may clearly prompt the proliferation of LX2 cells (hepatic stellate cell line), but without any effect on HepG2 cells in vitro [Hepatocellular carcinoma (HCC) is characterized by highly vascularized and rapid tumor progression which has been considered as the main reason for its devastating outcome. Proliferation of vascular endothelial cells plays an important role in tumor growth. Wei in vitro . Similar3.More and more studies have revealed that the level of serum GP73 has great value for diagnosis of hepatocellular carcinoma and several other cancers. The mechanisms responsible for this variability are still unknown. Several investigations have demonstrated that GP73 protein is overexpressed in a variety of acute and chronic liver diseases and its concentration was significantly correlated with the grading of liver fibrosis ,15. Howeet al. [We found that GP73 was down-regulated in hepatocytes early after HCV infection. HCV infection is associated with a complex dysregulation of the cytokine/chemokine network. Patients with chronic HCV infection are at risk for developing cirrhosis and HCC . Severalet al.  have shoC-terminus of E1A is required for GP73 expression [In normal livers, GP73 is considered to presenting in biliary epithelial cells, whereas hepatocytes show little or no expression of GP73 . Overexppression . Levels pression . CombineSince the high GP73 serum concentration was observed in patients with advanced liver disease and some tumors, which suggested that soluble GP73 may be playing a role in disease progression. Previous study has found that GP73 may obviously prompt proliferation of LX2 cells . We furtIn conclusion, GP73 is an interesting molecule that deserves further investigation. The molecular mechanism of up-regulation of GP73 in advanced liver disease still needs to be addressed. Moreover, researchers pointed out that increased expression of GP73 in hepatocytes appears to be a general feature of advanced liver disease, and may be regulated via distinct pathways that involve hepatotropic viruses or cytokines. Further studies are warranted to be able to assess the role of GP73 in the progression of liver disease.4.4.1.l-glutamine, 0.1 mmol/L nonessential amino acids (NEAA) and 1% penicillin-streptomycin . HepG2/CD81 was generated by overexpression of human CD81 in HepG2 cells [HEK 293T, HepG2, HepG2.2.15, Hep3B, Huh7, Huh7.5.1 and human umbilical vein endothelial cells (HUVEC) were grown under standard conditions in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum, 2 mM G2 cells .GP73 (GI: 7271866) and CXCL10 (GI: 323422857) were amplified from Huh7 cell cDNA by polymerase chain reaction (PCR). The forward and reverse primers used were shown in Encoding genes of Purified RNA or plasmids was transfected into HepG2, HUVEC or Huh7 cells using lipofectamin 2000  according to the manufacturer’s instructions.4.2.in vitro transcription kit  according to the manufacturer’s recommendations. Then these RNA were purified with tris-saturated phenol: chloroform: isoamyl alcohol (25:24:1). Before transfection 1.5% agarose gel electrophoresis was performed to check the integrity and purity of viral genome RNA.The plasmid pFL-J6JFH1  was first linearized by XbaI . The mixture was precipitated by 0.1 volumes of NaAc (3M pH = 5.2) and 2 volumes of Ethanol. The precipitation was resolved with diethyl pyrocarbonate (DEPC)-water, and used as templates to generate virus genome RNA using Cell-culture-derived HCV (HCVcc) were produced by transfection of Huh7 cells with HCV genome RNA as described . The sup4.3.For GP73 gene expression analysis, total RNA was isolated from cells using Trizol agent  and reverse transcribed to cDNA using the cDNA synthesis kit . Each cDNA sample was analyzed using the StepOnePlus real-time PCR system  using SYBR Premix ExTaq2  according to the manufacturer’s protocol. The primers used for gene expression analysis were shown in 4.4.4 cells/well). Twenty-four hours later, culture medium was removed and replaced with 500 μL fresh medium containing 150 μL of culture from 293T cells transfected with pcDNA-s-CXCL10 or mock vector control. Cells were incubated for 24 h and total RNA was isolated for RT-PCR analysis.CXCL10 were produced as described ,23. Brie4.5.v/v) conjugated to Alexa Fluor 488 . At last, cells were stained with 4,6-diamidino-2-phenylindole  and viewed using Immunofluorescence microscope .Immunofluorescence assay was performed as described . Briefly4.6.Cultured HUVEC cells were divided into three groups: transfected with recombinant pcDNA-GP73, transfected with pcDNA3.1 mock vector and untransfected cells. Cells were cultured in DMEM medium containing 10% fetal bovine serum and 350 mg/L G418 . Resistant clones could be detected two weeks later and were selected to further expand.Cell proliferation was monitored using Cell Counting Kit (CCK8) . HUVEC cells with overexpressing GP73 or control were allowed to grow in 96-well plates (3000 cells/well). Cell proliferation was measured at 12 or 24 h intervals following the manufacturer’s protocol. All experiments were performed in triplicates.4.7.p < 0.05.Data are presented as means ± standard error (SD). Statistical significance of differences was examined by one-way ANOVA and Dunnett’s test. All data were analyzed using the SPSS 18.0 computer program , and significant difference was defined as 5.in vitro. The chemokine CXCL10 was thought to induce decreased expression of GP73. CXCL10 stimulation leads to down-regulation of GP73 in Huh7 and HepG2 cells. Overexpression of GP73 in vascular endothelial cells had no impact on cell proliferation.In the present study, we identified that GP73 is down-regulated at the early stage of HCV infection while is up-regulated at advanced stage of HCV infection


The biological influence of light on human physiology  has long been recognized. Recent interest has been directed to understanding the ramifications of light on immune function, particularly in the context of patient care. Although light and seasonal variations have been shown to modulate leucocyte count and lymphocytes B and T activity and proliferation in mammals, little is understood about these interactions in the course of illness. Thus, we hypothesized that sunlight is directly associated with improved outcome in critically ill patients.2/day), a measure of solar energy striking a unit of earth surface area that was obtained from the National Aeronautics and Space Administration. Daily and total insolation was determined for each patient, accounting for hospital geographic location, period and duration of hospitalization, and adjusted by day-specific admission/discharge-sunrise/sunset times. To adjust for differences in case mix, we abstracted data regarding patient age, race, injury severity score, length of stay (LOS) and admission diagnostic categories. Patients who died before 24 hours were excluded from the analysis. The hypothesis was modeled using a multivariate logistic regression submodel for survival and a linear mixed submodel for the insolation measurement. Both were linked by the random intercept parameter in the mixed submodel.We conducted a retrospective, cohort study of all patients admitted to the ICU at a single center between the years 2000 and 2004. Light exposure was assessed by theoretical insolation (kWh/m2 (mean ± SD). After adjusting for differences in case mix, there was no significant association between survival and total insolation dose at 24 hours and up to the 10th day of ICU hospitalization (P = 0.64). A tendency towards lower mortality with higher insolation was observed for trauma patients (P = 0.15), although this did not attain statistical significance.A total of 22,730 patients were available for study. The majority was male (52.7%) and Caucasian (80.0%) with a mean age of 59.4 ± 17.7 years. The leading ICU admission diagnoses were cardiovascular conditions (23.4%), trauma (13.4%) and sepsis (5.9%). The mean APACHE III score was 52.8 ± 28.3, LOS was 3.3 ± 2.3 days and mortality was 13.4%. The total insolation per patient was 14.8 ± 33.2 kWh/mSunlight has no impact on general ICU patient survival according to our analysis. In other relevant outcomes , the impact of sunlight still has to be elucidated.


Plasmodium vivax is the predominant species causes of malaria with about 90% total annual reported malaria in Iran. This study conducted to determine the susceptibility of Plasmodium vivax isolates to chloroquine in Sistan and Balochistan Province, southeastern Iran.P. vivax infection completed the designed 28-day in vivo study. The thick and thin film blood smears were screened for malaria parasites by microscopy. The nested PCR was applied using the Plasmodium 18 subunit ribosomal ribonucleic (Ssr RNA) genes for detecting mixed infections and diagnosis of parasites in the samples with low parasite on days 0, 5, 6, 7, and 28.A total 270 subjects with symptomatic malaria and confirmed P. vivax was cleared in 15%, 50%, 95%, and 100% of patients on days 1, 2, 3, 4 respectively by microscopy assessment. Six patients were exhibited specific P. vivax band in nested PCR on day 5. No recurrence was observed on days 7, 14 and 28. Mean (±standard deviation) parasite clearance time was 2.41 (±0.8) days.P. vivax is still susceptible to chloroquine in Southeatern Iran. This finding is compatible with results of neighboring countries Pakistan and Afghanistan. Plasmodium vivax (P. vivax) is the main cause of malaria in Asian, Central and South American countries  has been reported in Iran  stephancy, A. culcificis, A. fluviatalis, A. superpictus and A. pulcherrimus are the main malaria vectors in the area  infection.A total of randomly 285 subjects with symptomatic malaria and confirmed P. vivax mono infection with parasite density above 250/µl, and fever or history of fever during 48 hours prior to the time of recruitment. Patients with the following conditions were excluded from the study: presence of clinical condition requiring hospitalization, presence of severe malnutrition, pregnancy, chronic infectious diseases, and concomitant febrile illnesses. All patients were followed up for 28 days according to the WHO in vivo test protocol . According to the Iran national drug policy, primaquine (PQ) is given during 8 weeks for preventing relapses. Since half-life time of chloroquine extends nearly 30 days and during this time it can eliminate emergent parasites , thus PQ administration was postponed to day 28. Inclusion criteria for the registered malaria patients were patients who aged more than 1 year old, positive for protocol . The patP. vivax, which required hospitalization in presence of parasitemia, presence of parasitemia and auxiliary temperature of ≥ 37.5 at any time between days 3 and 28, and presence of parasitemia between days 7 and 28 irrespective of clinical conditions. Blood samples were taken on days 0, 5, 6, 7, 28 and stored at -20°C until DNA extracting for nested PCR. The study protocol was approved by the Tehran University of Medical Sciences, Iran. The consent obtained from all participants or their parents.The treatment failure was defined as clinical deterioration due to 3 of blood. Genomic DNA was extracted from the 200µL blood samples using a QIA quick PCR purification kit  according to the manufacturer’s protocol. The nested PCR was applied using the Plasmodium 18 sub-unit ribosomal ribonucleic (Ssr RNA) genes for detecting mix infections and diagnosis of parasites in the samples with low parasite (less 10 P/µl). Primers and detail PCR amplifying method have previously been described  were male. chloroquine was well tolerated and no patient reported vomiting within 1h of drug administration. Fever resolved on the first day in all subjects. According microscopy findings ectively . No recuPlasmodium genus on day 0. All 270 subjects showed ∼120 Bp band in the nested PCR, which is indicative of P. vivax malaria  and SD were 2.43  and 0.8 days respectively. MPCT based on sex was 2.39 and 2.44 days in males and females, respectively. There was no significant difference regarding MPCT between males and females . The number of parasite ranged from 1,000 to 35,000 P/ µl blood with geometric mean of 7,500 P/µl.The PCR product was consider positive when a band of size of ∼1200 Bp was observed for  malaria . Six  and Afghanistan , where Preported , while nreported , 20. OurP. vivax still has suitable susceptibility to chloroquine in southeast of Iran and chloroquine can be administrated for treatment of the vivax malaria patients at this region. Nested PCR was also suitable assay to determine exact malaria parasite clearance time in our in vivo study.In conclusion,


Juvenile Dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in childhood, a systemic vasculopathy that affects usually skin, skeletal muscle, gastrointestinal tract and other organs. The diagnosis is made by criteria and the goals of treatment include control the underlying myositis and prevent disease and treatment complications. Stepwise aggressive treatment decrease long term sequelae and improve outcomes with a more rapid normalization of muscle inflammation.We studied demographics, epidemiology, clinical and laboratory characteristics in a descriptive observational study of 18 children with JDM assisted at our hospital from January 2000 to November 2010.72.2% of patients were females. Mean age at disease onset was 7.36 years. Most common presenting features were cutaneous and weakness. Medium time between first signs/symptoms and diagnosis was 59 days. 81.2% had pathological CK at diagnosis. CMAS was pathological in 85.7% of patients, electromyography in 84.61% and magnetic resonance image (MRI) in all patients that was made. Muscular biopsy was compatible with JDM in 83.33%. Medium time between first symptoms and treatment beginning was 1.94 months. Drugs more frequently used were corticosteorids, methotrexate, hidroxicloroquine and intravenosus immunoglobulines. Time to response was 7.12 months. 50% of patients had disease relapse  and medium time for it was 6.63 months. Actually, 7/16 patients have reached clinical remission, 6/16 complete clinical response, 2/16 clinical response.1. Other myositis-enzymes than CK should be tested at diagnosis.2. MRI could evaluate muscular edema with a no invasive technique.3. Muscular enzymes are a good tool to monitor disease activity but in some patients wonÂ´t be useful, so we have to consider MRI and other activity markers.


It has been considered that these deficits in neurocognitive function occur Alternatively the deficits could be caused by delayed diagnosis and inadequate early treatment. In Auckland, early diagnosis occurs via our newborn screening programme along with an aggressive high dose treatment paradigm following referral to the endocrine service. Thus we hypothesised that early diagnosis and aggressive therapy with close monitoring would result in normal neurocognitive outcomes.A blinded prospective sibling-matched study was undertaken. Subjects were otherwise healthy children and adolescents aged 4 to 18 years. Exclusion criteria for both CH subjects and sibling controls included chronic illness, other congenital problems or documented developmental delay, cerebral palsy or other disability. Assessments included WPPSI for children under 7 years old, WISC IV for children > 7 years and several tests of motor function including the Berry assessment of visual motor function, PPVT and ABC. Auxological data were collected and body composition was assessed using DEXA scans.49 children with CH and 53 sibling controls were recruited. Control subjects were younger (8.5 vs 10.4 years) but had similar gender proportions , height SDS (0.81 vs 0.84) and weight SDS (1.05 vs 0.97). In the CH group, 22% had athyreosis, 20% had dyshormonogenesis and 57% had ectopia. Average time to diagnosis was 12 ± 6.7 days and free T4 was normal by 16.6 ± 5.7 days. There was no difference in Verbal IQ between control and CH subjects (93.6 vs 96.7), Overall IQ (95.2 vs 95.1) although there was a trend to better processing speed in the control subjects . There was no difference between groups for motor function although there was a trend to better overall ABC scores in the CH group . There were no differences in body composition between the two groups although BMD trended to being lower in the CH group . There was no association with developmental outcomes and the age at diagnosis.Conclusion, the current Auckland diagnosis and treatment paradigm results in neurocognitive outcomes no different to siblings. BMD was lower in the CH group, possibly suggesting the children have been mildly over treated.


After calibration by thermodilution (TD), the PiCCO device is able to assess cardiac index (CI) using pulse contour (PC) analysis. The manufacturer suggests recalibration by TD after 8 hours. Recently, we suggested a calibration index indicating a certain probability of a relevant bias and triggering the next calibration. With changes of CIpc compared with the previous CItd being a key predictor of the bias of CIpc compared with the following CItd, the manufacturer implemented a soft alarm indicating changes in CIpc compared with the last CItd . The aim of the study was prospective evaluation of predictive capabilities of the 15% alarm regarding a bias of CIpc compared with CItd exceeding critical thresholds of 15%, 20% and 25%.A prospective analysis of 329 routine TPTD measurements in 70 patients. The CI-trend alarm was set to 15%, and CIpc, trend alarm (yes/no), relative and absolute changes in CIpc were recorded immediately before TD providing exact measurement of CItd. Predictive capabilities of the 15% trend alarm regarding the bias were evaluated using Spearman correlation, chi-square test, ROC analysis and Wilcoxon test (IBM SPSS 20).2 compared with the next CItd. Percentage error was 34.6%. Absolute and relative bias of CIpc compared with the new CItd did not correlate to time to last TD, but correlated  to CIpc itself  and relative  and absolute  changes in CIpc compared with last CItd. The 15% CIpc trend alarm was indicated before 83/329 measurements (25.2%). The amount of bias exceeded 15% and 20% in 101 (30.7%) and 79 (24%) of TDs. In TDs with indicated trend alarm (≥15% deviation of CIpc to the last CItd), the amount of bias more frequently exceeded 15% (P = 0.019), 20% (P <0.001) and 25% (P <0.001). Time to last calibration ≥8 hours was not associated with bias exceeding 15% (P = 0.735), 20% (P = 0.888) or 25% (P = 281).A total of 70 patients , age 62 ± 14 years, APACHE II score 19.5 ± 7.5, SOFA score 8.9 ± 4.4. At 937 ± 904  minutes after the last CItd, CIpc provided a bias of -0.0566 ± 0.761 l/ minute*mBias of CIpc compared with the next CItd does not depend on the time since last CItd. Changes in CIpc itself compared with the last CItd are associated with the bias. A 15% change in CIpc trend alarm provided by the new PiCCO algorithm is significantly associated with bias values exceeding 15%, 20% or 25% of CItd, whereas time to last calibration >8 hours is not associated with bias exceeding these critical thresholds.


Objectives: Given the need to ensure that dentists are sufficiently skilled to offer the best possible care to their patients, this study aims to evaluate the teaching methods and clinical experience achieved by undergraduate dental students in Spain and Portugal as regards complete dentures. Study design: In February 2011, a questionnaire seeking information about the preclinical and clinical teaching of complete dentures was e-mailed to all Spanish and Portuguese dental schools with fully developed undergraduate degree dental programs. Results: A response rate of 82.6% was obtained. The distribution of lectures and hours spent at the laboratory and in clinical activities revealed that teaching complete dentures is eminently a practical issue, this being mostly performed by full-time prosthodontists. All surveyed schools teach the design of the record base, and most of them instruct students in the mounting of teeth in wax. Most schools (94.7%) used a semiadjustable articulator, alginate for primary impressions (73.7%) and elastomeric materials in border-molded custom trays for final impressions (68.4%). In most schools, within the clinical setting students work in pairs, the mean student/ professional staff member ratio being 2.3 ± 0.7. Most schools perform a competence-based assessment (83.3%), although innovative techniques such as problem-based learning are still rarely applied. On average, the students emplaced 1.8 ± 1.2 complete dentures during their clinical training, ranging from 0 to 4, although no clear trend was seen as regards the minimum number of dentures to be made for graduating. Conclusions: Variations in teaching programs and clinical experience concerning complete denture curricula among Spanish and Portuguese dental schools are evident, but all the schools base their teaching mainly on preclinical and clinical practice. However, the low number of dentures made by student per year seems insufficient to ensure clinical skills and cope with social needs. Key words:Dental education, questionnaires, complete dentures, curricula. In 1970 Sharry .Clark  suggesteIt was also predicted that the number of students in dental schools would decline as the 21st century progressed. However, in Spain the number of dentists is in fact growing exponentially .It should be noted that operative dentistry and prosthodontics continue to be the two largest areas in dentistry , even inIn light of the need to ensure that dentists will be sufficiently skilled to offer the best possible care to their patients and for monitoring the baseline clinical competences among European countries according to the recent mandatory implantation of the Bologna Accord for Convergence in Higher Education in the European Union (settled for the academic year 2010-2011), the present study aims to evaluate the current situation regarding teaching methods for CD construction in Spain and Portugal and to determine which educational techniques and materials are currently used, before the implantation of the Bologna System. To date only U.S  and BritIn February 2011, a questionnaire was sent by e-mail to the chairperson identified as being responsible for the course in CD construction at each of the 23 dental Schools in Spain and Portugal. The questionnaire was designed to capture information concerning the curricular content of the teaching of CD for undergraduates before the implantation of the Bologna System. Following a second mailing to schools that had not replied to the initial attempt within two weeks, 19 of the 23 dental Schools  responded, affording a response rate of 82.6%.The questionnaire consisted of 22 items, and asked the respondents to specify several teaching aspects of their CD programs. Some questions were open, to acquire both quantitative and nominal data with freedom, while others were closed in either a dichotomous or in a multiple-choice format. However, even within these items, the option of providing a specific answer other than the choices listed was also available for some questions. The questions (Q) were pilot-tested by members of dentistry schools of both countries with experience in this field, who approved the questionnaire before it was mailed.Data were imported to SPSS v.18 for Windows , and descriptive statistical procedures were carried out to summarize the information.All schools still include CD teaching in their curricula, but there are considerable variations in the experience actually gained by students. The responses distribution to the questionnaire is summarized in -Preclinical teachingQ1: Preclinical course of tooth mounting and the design of prostheses.Seventeen schools (89.5%) reported that they systematically performed this kind of laboratory teaching in their CD curricula. One school reported that its teachers taught it occasionally (5.3%) and another school declared that it never did so (5.3%).Q2: In which academic year is your laboratory teaching implemented?Most schools offer preclinical teaching during the 3rd year (73.7%), but also during 4th year (15.8%) and even during the 5th year (10.5%), which is the last year for Spanish graduates and the penultimate year for Portuguese students.Q3: Total number of lectures, and hours spent at the laboratory and in clinical activities.The mean number of hours devoted to lectures was 24.2 ± 24.1, ranging from 2 to 110. The mean number of laboratory hours was 32.6 ± 25.6, ranging from 4 to 110 hours. The mean number of hours spent in clinical activities was 41.7 ± 44.1, ranging from 0 to 120 hours.Q4: How is the theoretical curriculum for CD taught?The mean number of hours of formal lectures (one professor teaching a class) was 22.5 ± 18.1, ranging from 5 to 80 hours. The mean number of hours devoted to tutorials and seminars was 15.7 ± 13.5, ranging from 1 to 45 hours. Other techniques, such as problem-based learning and e-learning were also used, with a mean number of hours of 4.2 ± 6.1 ranging from 0 to 15 hours.Q5: Student-to-professional staff member ratio in teaching CD.Eight schools (42.1%) reported a preclinical ratio of 10 or fewer students per staff member, and ten schools (52.6%) reported a ratio between 17 and 28 students per staff member. The mean ratio was 16.1 ± 7.3, in a range from 6 to 28 students. The student- staff member ratio for lectures was on average 55.8 ± 20.9 students, ranging between 25 and 100 students. For tutorials, the mean ratio was 7.2 ± 12.0 from a minimum of 1 to a maximum of 44 students. For clinical practice, the mean ratio was 10.9 ± 9.4, in the range of 5 to 40 students per staff member. Thus, the ratio decreases from lectures to tutorials.Q6: Prosthodontists teaching CD.Sixteen schools (84.2%) reported that the theoretical teaching of CD was implemented by full-time prosthodontists (professors or tenured lectured), but in the others the teaching was implemented by part-time prosthodontists. However, the practical teaching of CD is supervised by full-time prosthodontists in 63.2% of the schools, in the remaining 36.8% being supervised by part-time prosthodontists.Q7: Material used for laboratory teaching.The following results refer to dichotomous questions (Yes/No). Fourteen Schools (73.7%) reported using irreversible hydrocolloid as the preliminary impression material in edentulous Dentoform(TM) in manikin heads, and 63.2% reported making custom-trays, both self-cured and light-cured. All the schools surveyed teach students how to design the limits of acrylic record bases on the plaster model. Eleven schools (57.9%) reported using zinc oxide impression paste in custom trays for final impressions in preclinical teaching.Q8: Mandibular positioning in the centric relation.Eighteen schools (94.7%) used thumb and finger manipulation for positioning the mandible in the centric relation, but one school does not instruct students in jaw handling.Q9: Articulator used and settings.The following results refer to dichotomous questions (Yes/No). Eighteen schools (94.7%) reported using a semi-adjustable articulator in their clinical CD program, but only 15 schools (78.9%) use eccentric records to set the condylar trajectory and the Bennett angle of the articulator.Q10: Tooth assembly.The following results refer to dichotomous questions (Yes/No). Eighteen schools (94.7%) reported that their students make denture setups on wax. However the 73.7% of the surveyed schools instruct students to achieve a bilaterally balanced occlusion throughout occlusal adjustments and teeth-remounting. In this sense, 68.4% of the schools reported that their students are taught that customizing articulator parameters is essential for achieving a bilaterally balanced occlusion.Q11: Preclinical assessment.Fifteen schools (78.9%) perform a preclinical assessment of the competences achieved. Such assessments are only theoretical (31.3%), only practical (12.5%), or theoretical and practical (50.0%). Some criteria for such assessments have been explored in terms of relevance by schools that do carry out an examination, as follows. For example, the prosthetic prescription of the den-tures is considered to be important or very important by 76.9% of schools and to be unimportant according to the rest (23.1%). Record base retention is considered to be important by 92.9% of schools performing preclinical assessments. Moreover, the in-terocclusal records  are also considered to be important by most schools (92.9%). The same proportion of schools considers the assembly of models on an articulator, the tooth set-up technique, and occlusal equilibration to be important.-Clinical teachingQ12: In which academic year does clinical teaching start?Eleven schools (57.9%) start clinical training in the 4th or in the 5th year (36.8%). Only in one school do students start treating edentulous patients during their 3rd year (5.3%).Q13: Student-instructor ratio in clinical sessions and activities.The student-staff member ratio for clinical sessions was on average 10.6 ± 6.9 students, the range being between 5 and 30 students. In 14 schools , students work in pairs; in one school they work in threes, and in two schools 4 students work in the same box. The mean ratio for clinical activity was 2.3 ± 0.7 students/staff member.Q14: Material used for final impressions.Thirteen schools (68.4%) use custom trays instead of standard trays (31.6%) for making the final impression. Moreover, six schools (37.6%) use polyether as the primary material for final impressions and 5 responding schools use polyvinylsiloxane (31.3%) and another five schools (31.3%) mainly use alginates and/or zinc oxide pastes. Three schools (15.8%) did not respond to this item, and hence the previous percentages have been corrected accordingly.Q15: Competence-based exam for CD.Most of the 18 schools responding to this question (83.3%) reported that they do perform a competence-based assessment to see when the students are suitably prepared to treat CD patients, although most of them were still working on configuring a set of the most discriminative criteria for this assessment of competence.Q16: Final examination.Two schools did not respond to this item (10.5%). Of the other 17 schools, 41.2% gave a final exam comprising theoretical, preclinical and clinical sections. Four schools offered (23.5%) only a final written examination; three schools demanded both a pre-clinical and written final examination (17.6%); two schools carried out clinical and written examinations, and another school (5.9%) did not demand a final exam for CD.Q17: Minimum CD requirements for graduation.Eight schools (53.3%) indicated that students have ne-cessarily to make a minimum number of CDs in order to graduate, and 7 schools (46.7%) indicated that there was no such limit. On average, students constructed 1.8 ± 1.2 CD during their clinical training, ranging from 0 to 4. The distribution is shown in table 2. All the above values were estimated after correcting for the four non-responding schools (21.1%).Q18: Clinical procedures for CD.Thirteen of the 17 responding schools (76.5%) reported using a plastic compound as the primary material for border molding, whereas 4 (23.5%) declared no pattern in this customizing procedure. Among the same respondents, 9 schools (52.9%) reported that their students always performed a clinical remounting procedure and occlusal equilibration in the articulator before denture delivery, whereas 5 schools (29.4%) did so only in some cases, and 3 schools (17.6%) never.Q19: Materials used for making CD.Fifteen schools answered this item (78.9%) and indicated a percentage estimation of the materials used. On average, 88.7 ± 16.0 % of patients’ CD are made in acrylic, and the remaining 12.3 ± 15.7 %, are made in acrylic but with a metal reinforcement. Among these respondents (15 schools), 67.7% ± 44.0 % of the patients’ CD had anatomic teeth and 32.3% ± 42.4% had semi-anatomic teeth. Artificial teeth were mostly of acrylic (90.7% ± 25.8%) but also of ceramic in a lesser percentage (9.3% ± 25.8%).Q20: Clinical Relining procedures.Within the 17 responding schools, 9 (52.9%) indicated that their students are taught in relining denture bases but only using soft relining materials, and 3 (17.6%) with both hard and soft materials. However, in 5 schools (29.4%) the students never perform relining procedures.Q21: Articulator used and settings for clinical teaching.Within the 17 responding schools, five (29.4%) use Dentatus(TM) ; three (17.6%) use Stratos(TM) ; three (17.6%) use QuickMaster(TM) ; two (11.8%) use WhipMix(TM)-8500 ; two (11.8%) use Artex(TM) , and two (11.8%) use BioArt(TM)-4000 . However, only in 4 schools (23.5%) is the real axis of the condylar rotation located, and then only sometimes; the rest of the schools (76.5%) use an average axis.Q22. Virtual video demonstrations.Eighteen schools responded to this question (94.7%). Half of them declared that they had pre-recorded video demonstrations available for their students on the internet.The results of this survey demonstrate the broad variety in the ways of the teaching of CD among Spanish and Portuguese universities before the implantation of the Bologna System, although several trends in the materials and procedures used are detected. The main coincidence is that all the schools surveyed teach the design of the record base on the plaster model. Also, most schools (89.5%) have a preclinical course of tooth mounting and denture design, mainly implemented during the third academic year of their respective courses 73.7%). This preclinical course is widely applied in both U.S.  and Brit3.7%. ThiIn terms of quantitative teaching, the distribution of hours dedicated to lectures, laboratory work and clinical activities reveals that the teaching of CD is eminently a practical issue : Q3. TheAccording to Rashedi et al. , the oveStarting in 1970, some authors have documented the broad variations in student/professional staff ratios in Dental Schools (rang-ing from 1:3 to 1:33) . The stuThe percentage of full-time prosthodontists supervising CD teaching is similar to that reported by Rashedi et al.  for U.S.In terms of materials and procedures, most programs (95%) report using a semi-adjustable articulator and teaching jaw manipulation tests to establish the mandibular centric relation and eccentric records in order to customize the parameters of the articulator. The proportion of schools teaching a custom setting of semi-adjustable articulators instead of using average parameters is surprisingly high : Q9, as For impressions, in consonance with previous research carried out in the U.S. ,12 most Furthermore, most schools use custom trays for final impressions, although the percentage is lower than that reported among U.S. Schools (98%) . Most SpIt is noteworthy that although the Bologna Declaration Agreement has only been introduced recently, and this system has not already affected to the subject of Prosthodontics, most schools do apply a uniform system of competence assessment, and most of them include an evaluation of clinical or preclinical skills in their final examination : Q16. DeCurrent evidence suggests that there will be a need for CD to be made in Spain  for decaThe present study highlights the main descriptors of the teaching of CD in Spain and Portugal, although this is only based on the perceptions of instructors. Thus, there is clearly a need to contrast this information by incorporating the views of trainees and this should be addressed in future studies.


According to the National Health survey only 3% of the population has controlled hypertension. This study was designed to elucidate the knowledge about hypertension in hypertensive patients at three tertiary care centers in Karachi. Secondly we sought to compare the knowledge of those with uncontrolled hypertension and controlled hypertension.It was a cross-sectional study conducted at The Aga Khan University hospital (AKUH), Ziauddin Hospital (ZH) and Civil hospital, Karachi (CHK. All diagnosed Hypertensive patients (both inpatients and outpatients) coming to a tertiary care hospital in Pakistan aged > 18 years were included. Patients were categorized into 2 groups: controlled and uncontrolled hypertension based on their initial BP readings on presentation Uncontrolled Hypertension was defined as average BP ≥ 140/90 mm Hg in patients on treatment. Controlled Hypertension (HTN) was defined as average BP <140/90 mm Hg in patients on treatment. Standardized methods were used to record BP in the sitting position. Knowledge was recorded as a15 item question. Primary outcome was knowledge about hypertension.A total of 650 participants were approached and consented 447 were found eligible. 284(63.5%) were from Aga Khan University, 101(22.6) from Dow University of health sciences and 62(13.9) were from Ziauddin University. Mean (SD) age of participants was 57.7(12) years, 50.1(224) were men. Controlled hypertension was present in 323(72.3) and uncontrolled hypertension was present in 124(27.4). The total mean (SD) Knowledge score was 20.97(4.93) out of a maximum score of 38. On comparison of questions related to knowledge between uncontrolled and controlled hypertension, there was statistically significant different in; meaning of hypertension (p <0.001), target SBP(p0.001), target DBP(p 0.001), importance of SBP versus DBP, improvement of health with lowering of blood pressure (p 0.002), high blood pressure being asymptomatic (p <0.001), changing lifestyle improves blood pressure(p 0.003),hypertension being a lifelong disease (<0.001), lifelong treatment with antihypertensives(<0.001) and high blood pressure being part of aging(<0.001). On comparison of knowledge as a composite score between uncontrolled and controlled hypertensive; Mean (SD) score was 21.85(4.74) v18.67 (4.70) . On multivariate analysis; gender β (95% CI) 1.67 p <0.001, uncontrolled blood pressure; -2.70 p <0.001, Sindhi ethnicity; -1.79 p 0.01 and pukhtoon ethnicity; -2.72 p <0.001 were significantly associated with knowledge score.Knowledge about hypertension in hypertensive patients is not adequate and is alarmingly poor in patients with uncontrolled hypertension. More emphasis needs to be made on target blood pressure and need for taking antihypertensives for life to patients by physicians. Hypertension (HTN) is one of the most common medical disorders, associated with an increased incidence of all-cause and cardiovascular disease (CVD) mortality. Fifty-fAccording to the National Health Survey of Pakistan (NHSP) the prevalence of HTN amongst adults >15 yrs was 17.9% and amongst them only 3% had their BP under control as opposed to a prevalence of 28.7% and control of around 31% being reported from US. Hence tThe NHSP showed that 70% of all hypertensive in Pakistan are unaware if their condition. KnowledIt was a crossectional study conducted at three tertiary care hospitals in Karachi; Aga Khan Hospital, Ziauddin Hospital and Civil Hospital Karachi. The Aga Khan Hospital is a 577 bedded facility, which provides high quality of patient care in a broad range of secondary and tertiary services to over 50,000 hospitalised patients and to approximately 600,000 outpatients annually. It is located in the center of Karachi. The Ziauddin hospital is a 300 bedded hospital and is located in north of Karachi. The Civil hospital is a 1900 bedded public sector hospital located in center of Karachi. Population of different socioeconomic strata caters to these hospitals. The study was conducted in 2009–2010. All hypertensive patients (an average BP of ≥140/90 mm Hg or if the participant is taking antihypertensive medications) > 18 years of age presenting to the outpatient clinics were included. DiagnosPrimary outcome was knowledge score which was based on 15 item questions. Knowledge was also computed as a composite measure of sum of all the 15 item questions. These questions were developed by brainstorming with experts managing hypertension and who suggested that correct response of these questions can be counted towards having sound knowledge on hypertension (in patients). Questions regarding knowledge were asked and were marked on a scale of 1–5. . Data was also stratified on basis of control of hypertension. Uncontrolled hypertension was defined as average BP ≥140/90 mm Hg in no diabetic patients on treatment . ControlA total of 650 participants were approached; 350 in AKU, 150 in DUHS and 150 in ZMU.Of the total participants who were approached and who consented, 447 were found eligible%(n); 63.5(284) from Aga Khan University, 22.6(101) from Dow University of health sciences and 13.9(62) from Ziauddin University. Overall response rate was 71.52%; 81% in AKU, 80% in DUHS and 49.6% in ZMU.Mean (SD) age of participants was 57.712) years, 224(50.1) were men and 223(49.8) were women. In ethnicity 108(24.3) were of Muhajir ethinicity. In education, 208(46.5) had > 10 years formal education. Comorbid conditions are shown in Table 2 years, Outcome of knowledge is reported as percentage(n) and mean(SD) scores have also been computed. Table On comparison of individual item question in men and women%(n); 57.7(128) men and 35.5(78) women agreed that hypertension means high blood pressure , 93.5(203) man and 92.5(205) women agreed that hypertension can be dangerous , 79.4(177) men and 60.5(135) women said that systolic blood pressure (SBP) should be <140 mm hg , 78.6(176) men and 58.3(130) women said that diastolic blood pressure (DBP) should be < 90 mm hg , 26.7(58) men and 11.8(26) women said that both SBP and DBP are important to control  men and 91.2(197) agreed that lowering blood pressure improves health , 45.8(99) men and 33(71) women agreed that high blood pressure can be asymptomatic , 82.8(184)men and 84(186) agreed that changing lifestyle improves blood pressure , 76(166) men and 73.3(162) women agreed that hypertension is a lifelong disease , 77(174) men and 72.8(161) women agreed that antihypertensives have to be taken for life , 57.3(126) men and 50.4(112) said that high blood pressure is a part of aging  The mean (SD) knowledge score in men was 21.8(4.9) and in women was 20.07(4.8) .On comparison of demographics of patients with controlled and uncontrolled hypertension, there was statistically significant difference in; Mean (SD) age (59.05 years 11.2) v 54.33 years (13.4)p <0.001), gender ,> 10 years of formal education (38.7% v8.1% p <0.001). Comorbids and history of hospitalization is shown in Table 1.2 v 54.On comparison of questions related to knowledge, there was statistically significant different in; meaning of hypertension (p <0.001), target SBP (p0.001), target DBP (p 0.001), importance of SBP versus DBP, improvement of health with lowering of blood pressure p 0.002), high blood pressure being asymptomatic (p <0.001), changing lifestyle improves blood pressure (p 0.003), hypertension being a lifelong disease (<0.001), lifelong treatment with antihypertensives (<0.001) and high blood pressure being part of aging (<0.001)  was 21.85(4.74) v18.67 (4.70)  Knowledge score on most of individual item questions between the two group was significantly different Table .On univariate linear regression for outcome of knowledge score; β(95% CI) was 0.064 for age, 1.79 for gender,-1.93 for sindhi ethinicity, -1.66 for Punjabi ethinicity, -2.22 for balochi ethnicity, -2.84 for pukhtoon ethinicity, -0.95 for Muhajir ethinicity, -0.99 for education up to <5 years,-1.14 for < 10 years of education, 0.75 for >10 years of education, 0.47 for history of hospitalization for uncontrolled hypertension, -3.17 for having uncontrolled hypertension. However on multivariate analysis gender β(95% CI) 1.67 p <0.001,uncontrolled blood pressure; -2.70p <0.001,sindhi ethnicity; -1.79 p 0.01 and pukhtoon ethnicity; -2.72 p <0.001 were significantly associated with knowledge score (Table We are first to report a knowledge score in patients with hypertension belonging to three different tertiary care hospitals in Karachi, Pakistan. We found that overall knowledge scores in hypertensive patients was not up to the mark. Furthermore scores in patients with uncontrolled hypertension were significantly low. The lowest scores were obtained to questions related to importance of systolic blood pressure versus diastolic blood pressure, high blood pressure being asymptomatic and high blood pressure being an unavoidable part of aging. Factors associated with knowledge scores were male gender, having uncontrolled hypertension and ethnicity. Interestingly formal education did not show any relation with high knowledge scores in these hypertensive patients. This suggests that specific knowledge about disease is needed and just education alone may not suffice.Sufficient knowledge about hypertension in patients has been associated with greater medication adherence and better blood pressure control. SeveralGaps in knowledge have been reported with regard to risk factors associated with hypertension in 110 university students in a crossectional study conducted in Gulf region. Nationality, course of study, raised blood pressure, and history of diabetes showed significant association with good knowledge, however their net effect was not significant by the Adjusted Odds Ratio. We repoSimilar results have been reported from Karachi, Pakistan on hypertensive and normotensives,14. The Less than 75% of people prescribed drugs for hypertension continue using them after 6 months after initiation, and this is associated with an increased risk of hospitalization for cardiovascular problems. KnowledThe strength of this study is that it is multi centered study focusing on in depth analysis of knowledge regarding hypertension. It points out specific aspects on knowledge about hypertension, by taking care of which the hypertensives may have better blood pressure control. There are several limitations to this study. Firstly the results from this study cannot be generalized to the rural population in Pakistan. Hence similar studies need to me conducted in rural areas as well. Secondly the questionnaire used for knowledge assessment was not validated; however it was pretested before using. Thirdly blood pressure reading at a single occasion was used for classifying patients into controlled and uncontrolled hypertension. Fourthly we did not account for white coat effect while making this classification. Although the research staff was trained in recording the responses of the item questions, the possibility of a small percentage of interviewer bias cannot be completely ruled out. Additionally we did not measure compliance to antihypertensive therapy in this patient population. However adherence related questions were asked and will be reported elsewhere.Knowledge about hypertension in hypertensive patients is not adequate and is alarmingly poor in patients with uncontrolled hypertension. More emphasis needs to be made on target blood pressure and need for taking antihypertensives for life to patients by physicians. Alternatively group education of such patients needs to be tested as an intervention to improve knowledge on these aspects in addition to the risk factors of hypertension.The authors’ declare that they have no competing interests.AA was responsible for conceiving the idea, drafting the protocol and getting approvals, SSG, SL and ZAH were responsible for implementation data collection and entry of the study, AA and AAH were responsible in drafting, revising and proof reading of the study. All authors read and approved the final manuscript.Appendix A.Click here for file


The impact of telemedicine application on the management of diabetes patients is unclear, as the results are not consistent among different studies. The objective of this study is to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the impact of telemedicine interventions on change in hemoglobin A1c (HbA1c), blood pressure, LDL cholesterol (LDL-c) and body mass index (BMI) in diabetes patients.Electronic databases MEDLINE, Cochrane Central Register of Controlled Trials and LILACS were searched to identify relevant studies published until April 2012, supplemented by references from the selected articles. Study search and selection were performed by independent reviewers. Of the 6.258 articles retrieved, 13 RCTs (4207 patients) were included. Random effects model was applied to estimate the pooled results.Telemedicine was associated with a statistically significant and clinically relevant absolute decline in HbA1c level compared to control . LDL-c was reduced in 6.6 mg/dL , but the clinical relevance of this effect can be questioned. No effects of telemedicine strategies were seen on systolic (-1.6 mmHg and 95% CI -7.2 to 4.1) and diastolic blood pressure (-1.1 mmHg and 95% CI -3.0 to 0.8). The 2 studies that assessed the effect on BMI demonstrated a tendency of BMI reduction in favor of telemedicine.Telemedicine strategies combined to the usual care were associated with improved glycemic control in diabetic patients. No clinical relevant impact was observed on LDL-c and blood pressure, and there was a tendency of BMI reduction in diabetes patients who used telemedicine, but these outcomes should be further explored in future trials. Diabetes mellitus (DM) has taken epidemic proportions throughout the world and is considered among the most challenging health problems in the 21st century ) vs. -0.44% (-4.8mmol/mol) (95% CI -0.74 to -0.15% [-8.1 to -1.6 mmol/mol]), p=0.039.It was impossible to stratify patients regarding baseline HbA1c because patient-level analyses were not performed. Studies with an average baseline HbA1c equal to or higher than 8.0% [64.0 mmol/mol] were compared to the ones with an average lower than 8.0% and demonstrated a higher impact of telemedicine in the first group: -0.64% (7.0mmol/mol) (95% CI -0.93 to -0.35% [-10.2 to -3.8 mmol/mol]) vs. -0.26% (-2.8 mmol/mol) (-0.43 to -0.10% [-4.7 to -1.1 mmol/mol]), p=0.027.Interventions which included changes in patient prescription through telemedicine  were associated with a more pronounced HbA1c reduction than the ones which did not : -0.75% (-8.2 mmol/mol) (95% CI -1.05 to -0.43% [-11.5 to -4.7 mmo/mol]) vs. -0.30% (-3.3 mmol/mol) (95% CI -0.45 to -0.14% [-4.9 to -1.5 mmol/mol]), p=0.013.Studies in which the intervention was made by physicians  were compared to the ones in which it was made by nurses , and revealed no difference in HbA1c change: -0.53% (-5.8 mmol/mol) (95% CI -0.94 to -0.13% [-10.3 to -1.4 mmol/mol]) vs. -0.43% (-4.7 mmol/mol) (95% CI -0.64 to -0.22% [-7.0 to -2.4 mmol/mol]), p=0.654.There was a tendency of a higher HbA1c reduction in interventions which lasted 6 months  when compared to the ones that lasted at least one year : -0.57% (-6.2 mmol/mol) (95% CI -0.85 to -0.30% [-9.3 to -3.3 mmol/mol]) vs. -0.30% (-3.3 mmol/mol) (-0.48 to -0.11% [-5.2 to -1.2 mmol/mol]), p=0.099.The subject impression of the funnel plot test suggested an asymmetry . Toward This systematic review  indicates that in diabetes patients, telemedicine strategies concomitant to the usual care are associated with a mean HbA1c decline of −0.44% (-4.8 mmol/mol) when compared to the usual care alone. HbA1c is recognized as a valuable indicator of treatment effectiveness in patients with diabetes ,15. AddiThe lack of a clinical significant impact on LDL-c and the absence of impact on blood pressure should not be interpreted as a definite finding. Regarding hypertension, a recent RCT which included a large sample of hypertensive patients (7.3% of them had diabetes) who were willing to monitor their blood pressure and self-titrate medication has shown that self-management of hypertension in combination with telemonitoring of blood pressure measurements resulted in significant reduction in blood pressure in 6 and 12-month follow-up when compared to usual care . No studOur findings also demonstrated that the impact of telemedicine strategies in reducing HbA1c was more pronounced in diabetes type 1. Type 1 diabetes patients are unique in that they have absolute insulin deficiency and consequently the have more pronounced glycemic variability than type 2 diabetes patients . Their mInterventions which included changes in patient prescription through telemedicine were associated with a greater benefit on HbA1c reduction than the ones which did not, and there was no difference regarding intervention made by physicians or nurses. These findings are important to address recommendations on telemedicine design strategies in clinical practice. The lack of difference between physicians and nurses impacts significantly in decreasing the costs of the intervention if applied to the healthcare system.Another important finding was the tendency of a higher HbA1c reduction in interventions which lasted 6 months when compared to the ones that lasted at least one year. Although it did not reach statistical significance, it suggests a trend of decreasing intervention impact over time. This finding suggests that in clinical practice contact through telemedicine and positive motivation should be intensified over time, in order not to decrease the impact on glycemic control. Additionally, a more participatory design approach, involving target users in developing personalized interventions, might enhance persistence in usage and adherence to treatment .This study was a rigorous systematic literature review that focused exclusively on RCTs in which telemedicine strategies included a personalized feedback from a healthcare practitioner to the patient or to other healthcare provider. Although only 5 studies had blinded assessment of outcomes, the outcomes were objective measures, with a low risk of bias in their assessment.Previous systematic reviews with less methodological rigor have not performed meta-analysis or failed to detect a significant impact of different telemedicine strategies on glycemic control ,26,30-32The evidence presented here could support the implementation of telemedicine in the care of diabetes patients. It has already been shown that telemedicine help improving patient care and access to specialized care, in particular in rural areas with limited accesses to health care facilities , and it In order to make these results applicable to clinical practice, it is also important to take into account that telemedicine may not be appropriate for all patients. There are some factors that are described as important elements for the success, such as awareness of the significance of the disease and its consequences, willing to participate actively in the treatment and in preventing complications and positive motivation . PatientThe main limitation of this meta-analysis is the heterogeneity. To address this, we have performed analyses to identify clinical and methodological differences between studies. Some factors could not be addressed, as the type of telemedicine intervention, because it was too diverse among studies. As the analyses were not based on individual data, it was not possible to stratify according to the basal HbA1c, and it is expected a higher impact in individuals with poor metabolic control. The inclusion of patients with good metabolic control may have underestimated the impact of the intervention, so it could be expected an even better result if we could stratify by the baseline HbA1c levels. The subgroup analysis comparing studies with an average HA1c lower or higher than 8.0% (64.0 mmol/mol) is limited, because it is not possible to effectively separate individuals with better and worst metabolic control. However, as it demonstrated a significantly higher impact on HbA1c in the subgroup of studies with baseline HbA1c equal to or higher than 8.0%, it provides an estimative of a higher impact of the intervention in patients with worst metabolic control.Although there was evidence of publication bias, trim-and-fill method revealed that publication bias did not interfere with the interpretation of results, as the imputed effect size was similar to the original effect, suggesting that the apparent publication bias is insufficient to affect our results or interpretations in a meaningful way.It is important to note that the endpoint HbA1c has some limitations. As a mean, it may show normal results in individuals who alternate hypo and hyperglycemias . BesidesIn conclusion, this systematic review and meta-analysis has shown that telemedicine strategies combined with the usual care are associated with improved glycemic control in diabetic patients. In this review, there was no clinical relevant impact on LDL-c and blood pressure, and there was a tendency of BMI reduction in diabetes patients who used telemedicine, but the impact on these outcomes should be further explored in future trials.A logical next step for future trials would thus be to assess whether the improved glycemic control observed with telemedicine interventions will translate into improved clinical outcomes. The optimal design of telemedicine systems is uncertain, so future research should also focus on what type of telemedicine intervention has the largest impact on diabetes management, and how to adapt systems to the individual patient needs and resources of specific health care systems. The evaluation of the cost-effectiveness of the intervention should also be addressed, which is relevant to decision makers and impacts on the applicability of the evidence in clinical practice. Checklist S1PRISMA checklist.(DOC)Click here for additional data file.


Endometrial cancer is strongly associated with body mass index (BMI), but the influence of BMI history and of different types of obesity is uncertain.M A case–control study was carried out in Italy including 454 cases and 908 controls admitted to hospital for acute non-hormone-related conditions. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using multivariate logistic and spline regression models.−2 was 4.08 (95% CI: 2.90–5.74). The association for BMI was monotonic with a possible steeper increase for BMI above 28. Conversely, waist-to-hip ratio (WHR) showed a bell shaped curve with increased OR  in the intermediate tertile only. After stratification by BMI at diagnosis, history of weight loss and BMI at age 30 did not influence endometrial cancer risk. History of obesity in middle age had a weak and not significant adverse effect among obese women .The OR for BMI >30 at diagnosis compared with 20 to <25 kg mThe predominant importance of recent weight compared to lifetime history, justifies encouraging weight reduction in women at any age. Endometrial cancer is strongly associated with overweight and obesity  at diagnosis, there is little additional excess risk of endometrial cancer in relation to history of overweight . In someTo further explore these issues, we used data on BMI at different ages and measures of waist and hip at diagnosis from a case–control study on endometrial cancer carried out in different parts of Italy . The interviewers measured the circumference of the waist (2 cm above the umbilicus) and hip  at the time of interview and computed WHR. Waist-to-height ratio (WHtR) was also computed. Waist or hip could not be measured in 89% of women interviewed in Milan centre, leading to a lack of information for WHR and WHtR in 33% of cases and 35% of controls. However, in the overall study, median BMI in women with a measured WHR was not substantially different from that in women for whom the information on WHR or WHtR was missing .Centrally trained staff interviewed eligible women during their hospital stay. Less than 5% of the approached cases and controls refused the interview. The response rates were similar across hospitals and geographic areas. All interviews were conducted using a structured questionnaire, which included information on age, education and other socioeconomic factors, physical activity, smoking habit, alcohol intake, a validated food frequency questionnaire, a problem-oriented medical history, and history of cancer in first degree relatives. In a detailed section of the questionnaire, women were asked to report their height and weight at 1 year before cancer diagnosis or interview , weight at age 30 and 50 years, lifelong highest and lowest weight, and perceived body size at age 12 years . BMI was computed as weight divided by squared height (kg m−2) were used to facilitate comparisons with previous studies. Tertiles obtained from the combined distribution of cases and controls were used to assess other anthropometric measures. A conditional logistic regression model was used to compute odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). All analyses were conditioned on age and study centre and adjusted for calendar period of interview, years of education, smoking habits, age at menarche and at menopause, parity, and use of oral contraceptives and hormone replacement therapy. Additional adjustment for alcohol intake, and occupational and recreational physical activity did not materially modify the risk estimates. To avoid potentially arbitrary categorisations, the ‘dose–risk’ relationship between BMI at diagnosis or WHR and endometrial cancer risk was assessed using logistic cubic regression splines , the ORs were 0.56 (95% CI: 0.27–1.15) in women with BMI <20, 1.41 (95% CI: 1.05–1.90) and 4.08 (95% CI: 2.90–5.74) in women with BMI 25 to <30 and BMI ⩾30, respectively. OR was 1.45 (95% CI: 1.06–1.98) among women who reported to have been heavier than their peer group at age 12 years. Compared with BMI 20 to <25, the OR for BMI ⩾30 at age 30 was 1.78 (95% CI: 1.01–3.14), and 3.37 (95% CI: 2.26–5.04) for BMI⩾30 at age 50 , but the association disappeared by adjustment for BMI at diagnosis .The distribution of endometrial cancer cases and controls, and the corresponding ORs, according to height, weight, BMI at diagnosis and at different ages are shown in t age 50 . Decreasvs <84 cm: 2.68; 95% CI: 1.78–4.03), hip circumference , and WHtR . No linear trend in risk, however, was observed for WHR. Compared with the lowest WHR tertile (<0.833), the OR was 2.10 (95% CI: 1.43–3.09) in the intermediate tertile but 1.33 (95% CI: 0.89–1.97) in the highest tertile (⩾0.890).vs 20 to <25=4.94; 95% CI: 3.38–7.23) than among pre- and peri-menopausal women , though this difference was not statistically significant .The shapes of the best-fitting regression splines for BMI and WHR are shown in vs <25 was 1.24 (95% CI: 0.49–3.13) and 1.59 (95% CI: 0.71–3.52) at ages 30 and 50 years, respectively. Among women with BMI ⩾30 at diagnosis, the ORs were 1.23 (95% CI: 0.54–2.82) and 1.60 (95% CI: 0.52–4.96) for a BMI ⩾30 vs <25 at ages 30 and 50 years, respectively. No association of perceived body size during adolescence and endometrial cancer emerged after stratification for BMI at diagnosis (data not shown).Our case–control study confirms the strong relationship between weight and BMI at diagnosis and endometrial cancer risk, especially among post-menopausal women. The effect of BMI did not show a lower threshold: but the risk curve became steeper among severely overweight women (BMI >28). After adjustment or stratification by BMI at diagnosis, history of weight loss and BMI in young adulthood did not influence endometrial cancer risk. History of obesity in middle age had, however, a weak nonsignificant adverse effect among obese women aged 50 years or older. These findings provide indirect support to the possibility of weight excess acting as late-stage carcinogens . The assThe relationship between endometrial cancer risk and WHR is less clear. A meta-analysis of one cohort study and four case–control studies provided a summary risk estimate of 1.45 (95% CI: 1.00–2.09) for an increase of 0.1 WHR units . In the WHtR is another measure of abdominal adiposity that has been only rarely used in endometrial cancer studies  per 5 BMI unit increase, based on three cohort studies. The corresponding value, based on six case–control studies, was 1.10 (95% CI: 0.95–1.27; No association or a weak direct association has been reported between height and endometrial cancer risk (Case–control studies may be subject to selection and information bias . HoweverIn our study, weights during lifetime and height were self-reported. It is known that most individuals, and especially those overweight, tend to underestimate their weight . ConversConfounding was dealt with in our study by adjusting for a broad range of risk correlates, including reproductive and hormone-related factors. Less than 6% of women reported any use of lifetime hormone replacement therapy for 2 or more years (The implications of this report from a public health viewpoint are clear. The fraction of endometrial cancer cases attributable to overweight and obesity in our study population was of 41% (95% CI: 31–51%


Perioperative symptoms such as pain and anxiety are common in spite of standard of care. Such symptoms are associated with a negative surgery experience, and moreover, are correlated with increased perioperative morbidity. The aims of this study were to evaluate whether acupuncture as an add-on to standard of care improves these symptoms. In addition, we assessed whether outcomes are correlated with expectations from CAM.We conducted a pragmatic trial of 479 adult patients undergoing various abdominal operations. Eighty-nine patients received standard medical care, and 390 patients received acupuncture on top of standard medical care, according to patient preference and practitioner availability. Numeric VAS scores for anxiety, pain, nausea and well-being were collected pre and post treatment. Acupuncture was provided according to Traditional Chinese Medicine syndrome categorization.There was a significant reduction of VAS scores for all outcomes in the acupuncture group: Anxiety scores were reduced from 4.4 to 2.6 , pain from 4.8 to 2.5 , nausea from 2.7 to 1.4  and well-being improved from 5.1 to 6.8 . Symptomatic improvement was significantly better in the acupuncture group as compared to the standard of care group for all parameters p<0.0001. In the subgroup of patients experiencing moderate to severe symptoms, improvement was even more prominent: anxiety scores were reduced from 6.9 to 3.8 ; pain from 6.9 to 3.6 ; nausea from 7.2 to 3.3 ; and well-being improved from 3.7 to 6.2 . We did not find a correlation between outcomes and patients’ expectations regarding acupuncture.Our results demonstrate that acupuncture therapy significantly improved common symptoms in patients undergoing surgical interventions.