Early invasive management and the use of combined antithrombotic therapies have decreased the risk of recurrent ischaemia in patients with acute coronary syndrome (ACS) but have also increased the bleeding risk. Transradial intervention (TRI) and bivalirudin infusion compared to transfemoral intervention (TFI) or unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decrease bleeding complications in patients with ACS. To what extent, a bleeding preventive strategy incorporating at least one of these two treatment options translates into improved outcomes is a matter of debate. The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX study is a large-scale, multicenter, prospective, open-label trial, conducted at approximately 100 sites in Europe aiming to primarily assess whether TRI and bivalirudin infusion, as compared to TFI and UFH plus provisional GPI, decrease the 30-day incidence of death, myocardial infarction or stroke across the whole spectrum of ACS patients.

OBJECTIVE

The objective of this study was to compare door-to-balloon times and other variables in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) using transfemoral or transradial approaches.

BACKGROUND

Transradial PCI has been shown to lower the risk of access site complications but the procedure is not applied to STEMI patients, due to concerns of procedural complexity adversely affecting prompt reperfusion. There is paucity of real-world data comparing TRI with TFI in patients with STEMI.

METHODS

Three hundred sixteen consecutive patients with STEMI undergoing primary PCI were studied. Patients were divided in two groups, Group I (n = 204) undergoing PCI transfemorally and Group II (n = 109) patients transradially. Demographic data, door-to-balloon times, procedural variables, predischarge adverse events, access site complications, and 1 year follow-up major adverse cardiac events (MACE) were recorded.

RESULTS

Door-to-balloon time was 72 +/- 14 min in Group I compared with 70 +/- 17 min in Group II, the difference was not statistically significant (t = 1.096, P>> 0.27). Group II patients had significantly fewer access site complications compared with Group I (20 vs. 1 patient, chi(2) = 10.8, P < 0.05). Demographics, predischarge adverse events, and MACE at 1 year follow-up were comparable between the two groups.

CONCLUSIONS

Transradial approach to primary PCI provides similar door-to-balloon times to transfemoral approach, and significantly lowers access site related complications, in patients presenting with STEMI.

BACKGROUND

Early percutaneous coronary intervention (PCI) following thrombolysis may be beneficial in patients with ST-segment elevation myocardial infarction (STEMI) who were admitted at a non-PCI hospital. The aim of this study was to evaluate the safety and efficacy of the radial artery as a vascular route for early PCI following thrombolysis in patients with STEMI.

METHODS

All consecutive STEMI patients within 12 hours after thrombolysis were enrolled, and eligible patients were randomly assigned to either transfemoral (TFI group) or transradial catheterization (TRI group). Several time intervals were measured. The puncture success rate and ambulation time were assessed. The vascular access-site complications were also assessed after the PCI procedure, and the incidence of major adverse cardiac events (MACE) in hospital was observed.

RESULTS

A total of 119 cases were enrolled, with 60 in the TRI group and 59 in the TFI group. There were no significant differences in transfer time and total procedure time. The puncture time in the TRI group was not significantly different compared to the TFI group. The time between PCI and ambulation in the TRI group was shorter than in the TFI group. There was a trend toward lower in the incidence of bleeding complications and vascular complications in the TRI group.

CONCLUSIONS

TRI for STEMI patients following intravenous thrombolysis was as safe and feasible as TFI, with a trend toward lower incidence of bleeding complications and vascular complications.

OBJECTIVE

To describe normative dental treatment needs of 5-7 and 12-year-olds in a rural sub county of Uganda and devise a strategy to improve oral health.

METHODS

Clinical survey.

METHODS

Primary schools in the subcounty.

METHODS

School-based random cluster sample of 236 5-7-year-olds and 202 12-year-olds. Dental status and treatment need data were collected according to WHO Oral Health Surveys Basic Methods. Additional data for 12-year-olds included dental fluorosis using the Thylstrup and Fejerskov index (TFI), oral hygiene procedures and experience of oral pain in the previous month.

RESULTS

In the 5-7-year-olds, mean dmft was 1.47 (50.8% dmft = 0). A total of 52.5% needed fillings and almost one third needed a tooth extracted. Among the 12-year-olds, mean DMFT was 0.64 (65.8% DMFT = 0), 28.5% had dental fluorosis and 6.7% had TFI>> 2. Toothache in the previous four weeks was reported by 36.5%, 30.2% needed a filling and 6.4% needed one or more teeth extracted.

CONCLUSIONS

Dental disease is a significant public health problem in this population. An efficient way to meet the needs of the children would be to increase the availability of fluoride toothpaste and to develop a service to provide treatment using Atraumatic Restorative Technique.

OBJECTIVE

To estimate the proportion of tubal factor infertility (TFI) caused by Chlamydia trachomatis (CT), the etiologic fraction, from a retrospective study of CT antibody prevalence in TFI cases and controls, adjusted for sensitivity and specificity.

METHODS

We use published data on sensitivity and specificity to estimate the performance of assays in (a) women with a previous CT infection without sequelae and (b) women with TFI caused by CT. A model was developed and applied to antibody prevalence in TFI cases and controls from 1 published case-control study to estimate the proportion of TFI caused by CT.

RESULTS

The proportion of TFI episodes that were due to CT infection was estimated to be 45% (credible intervals: 28%, 62%). Models which assume that test sensitivity is higher in women with CT-related TFI than women with previous infection and no sequelae fit the data significantly better than models that assume the same sensitivity in all those previously infected.

CONCLUSIONS

Greater attention needs to be paid to methods for characterizing the performance of CT antibody tests. Serological studies could be given a greater role both in CT etiology and in monitoring the effects of prevention and control programmes.

Sex hormones are involved in the carcinogenesis of some gynecologic cancers, and the status of their receptors represents an indicator of prognosis and of the therapeutic response in breast and endometrial cancers. In the ovary, this role is not clearly defined, with epithelial cancers being poorly responsive to hormone therapy. COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) is an orphan nuclear receptor, which is expressed in various tissues and regulates the estrogen receptor (ER) by competition for DNA binding. To investigate the role of these receptors in ovarian carcinogenesis and their implications for cancer prognosis, we evaluated the immunohistochemical expression of ER, progesterone receptor (PR) and COUP-TFI in benign and malignant ovarian epithelial neoplasms and in normal ovaries. A total of 113 ovarian specimens, including 40 diagnosed as malignant epithelial neoplasms (group A), 45 as benign epithelial tumors (group B), and 28 from normal ovaries (group C) were analyzed. Immunoexpression of ER was observed in 70% of patients of group A, 57.8% of group B and 57.1% of group C, with no significant difference between groups (p=0.426). Immunoexpression of PR was significantly lower in group A (12.5%) compared to group B (42.2%) and group C (32.1%) (p=0.010). Similarly, COUP-TFI was expressed in only 10% of group A patients, a rate significantly lower than that observed for group B (31.1%) and group C (39.3%) (p=0.014). No association was observed between the expression of these markers and increased survival or clinical prognostic variables. Multivariate analysis revealed a residual tumor <1 cm as the most significant clinical prognostic factor in group A (p=0.010, OR=4.14). These data support the importance of cytoreduction in the treatment of ovarian cancer, the role of steroid receptors in the mechanism of carcinogenesis, and the need for selection of subgroups that may respond to hormone therapy.

We examined meal patterns after isocaloric duodenal infusions of fat, carbohydrate (CHO), and protein by measuring meal size, intermeal interval (IMI) and total food intake (TFI). Wistar rats were adapted to normal feeding 6 h/day, with continuous computer monitoring of feeding patterns. One of five solutions (10 ml of 1 kcal/ml at 0.45 ml/min; 0, 20, 50, 80, or 100% of energy from fat) or saline (control) was infused 10 min after initiation of eating. Separate rats received casein or casein hydrolysate at 18.5 or 37% energy. Equivalent energy loads varying in fat, CHO, and protein content compared with saline resulted in similar reductions in first meal intakes. The second meal did not differ among fat and CHO treatments including saline; however, infusion with a protein-containing solution increased the size of meal 2. The IMI was doubled by protein infusion independently of dose or source but extended dose dependently by fat. TFI was lower after high fat and higher after protein than after saline infusion. The results indicate that the concentrations of fat, CHO, and protein differentially affect the qualitative and quantitative aspects of feeding in rats.

Since Waddlia chondrophila is closely related to Chlamydia trachomatis, we hypothesise that W. chondrophila may also be associated with tubal factor infertility (TFI) in women, a major complication of chronic C. trachomatis infection. Five hundred twenty serum samples were tested for anti-Waddlia antibodies by ELISA. Among the 520 investigated women, a total number of 142 (27.3%) has had laparoscopic diagnosis performed, and were either classified TFI positive or negative. Presence of high titres of W. chondrophila antibodies was linked to TFI (p < 0.0001; OR: 7.5; 95% CI: 3.3-17). Moreover, antibody positivity to both W. chondrophila and C. trachomatis-MOMP was strongly associated with TFI (p < 0.0001; OR: 21; 95% CI: 3.8-12E1). This association was much stronger than the statistical association of C. trachomatis-MOMP antibodies only (p < 0.0001; OR: 7.1; 95% CI: 3.7-14), suggesting that co-infection with W. chondrophila and C. trachomatis may lead to more severe reproductive sequelae and immune responses than single infection with either Chlamydiales members.

BACKGROUND

Transradial percutaneous coronary intervention (PCI [TRI]) does not involve catheter manipulation in the descending aorta, whereas transfemoral PCI (TFI) does. Therefore, the risk of acute kidney injury (AKI) after PCI might be influenced by vascular access site. We compared risks of AKI and nephropathy requiring dialysis (NRD) among patients treated with TRI and TFI.

RESULTS

We included patients across 47 hospitals in Michigan. Primary end point was AKI (serum creatinine increase ≥0.5 mg/dL). Secondary end points were NRD and postprocedural bleeding. Odds ratios (OR) for study end points were calculated for the entire and propensity-matched population, reported as crude, and values adjusted for preprocedural calculated AKI risk. Between 2010 and 2012, a total of 82 225 PCI procedures were performed, of which 8915 were TRI. After adjustment, TRI was associated with a reduction in AKI (OR, 0.76, 95% confidence intervals [0.62-0.92]) and bleeding with a trend toward lower NRD risk. The propensity-matched population consisted of 8857 procedures per group. In this population, TRI was associated with lower adjusted odds of AKI (OR, 0.74; 95% confidence intervals [0.58-0.96]), and bleeding (OR, 0.47; 95% confidence intervals [0.36-0.63]), but no difference in NRD was observed. Although postprocedural bleeding was independently associated with AKI (OR, 2.86; 95% confidence intervals [1.75-4.66]) in the propensity-matched population, the lower odds of AKI was not mediated by a reduction in bleeding with TRI. Sensitivity analysis demonstrated that the observed association between access site and AKI could potentially be explained by a moderately strong unknown confounder.

CONCLUSIONS

The risk of AKI was significantly lower after TRI compared with TFI. This finding needs to be evaluated in randomized controlled trials.

Background: Due to the lack of objective measures for assessing tinnitus, its clinical evaluation largely relies on the use of questionnaires and psychoacoustic tests. A global assessment of tinnitus burden would largely benefit from holistic approaches that not only incorporate measures of tinnitus but also take into account associated fears, emotional aspects (stress, anxiety, and depression), and quality of life. In Sweden, only a few instruments are available for assessing tinnitus, and the existing tools lack validation. Therefore, we translated a set of questionnaires into Swedish and evaluated their reliability and validity in a group of tinnitus subjects. Methods: We translated the English versions of the Tinnitus Functional Index (TFI), the Fear of Tinnitus Questionnaire (FTQ), the Tinnitus Catastrophizing Scale (TCS), the Perceived Stress Questionnaire (PSQ-30), and the Tinnitus Sample Case History Questionnaire (TSCHQ) into Swedish. These translations were delivered via the internet with the already existing Swedish versions of the Tinnitus Handicap Inventory (THI), the Hospital Anxiety and Depression Scale (HADS), the Hyperacusis Questionnaire (HQ), and the World Health Organization Quality of Life questionnaire (WHOQoL-BREF). Psychometric properties were evaluated by means of internal consistency [Cronbach's alpha (α)] and test-retest reliability across a 9-week interval [Intraclass Correlation Coefficient (ICC), Cohen's kappa] in order to establish construct as well as clinical validity using a sample of 260 subjects from a population-based cohort. Results: Internal consistency was acceptable for all questionnaires (α>> 0.7) with the exception of the "social relationships" subscale of the WHOQoL-BREF. Test-retest reliability was generally acceptable (ICC>> 0.70, Cohens kappa>> 0.60) for the tinnitus-related questionnaires, except for the TFI "sense of control" subscale and 15 items of the TSCHQ. Spearmen rank correlations showed that almost all questionnaires on tinnitus are significantly related, indicating that these questionnaires measure different aspects of the same construct. The data supported good clinical validity of the tinnitus-related questionnaires. Conclusion: Our results suggest that most Swedish adaptations of the questionnaires are suitable for clinical and research settings and should facilitate the assessment of treatment outcomes using a more holistic approach by including measures of tinnitus fears, emotional burden, and quality of life.

Tubal factor infertility (TFI) accounts for more than 30% of the cases of female infertility and mostly resides from an inflammatory process triggered by an infection. Clinical appearances largely differ, and very often infections are not recognized or remain completely asymptomatic over time. Here, we characterized the microbial pattern in females diagnosed with infectious infertility (ININF) in comparison to females with non-infectious infertility (nININF), female sex workers (FSW) and healthy controls (fertile). Females diagnosed with infectious infertility differed significantly in the seroprevalence of IgG antibodies against the C. trachomatis proteins MOMP, OMP2, CPAF and HSP60 when compared to fertile females. Microbiota analysis using 16S amplicon sequencing of cervical swabs revealed significant differences between ININF and fertile controls in the relative read count of Gardnerella (10.08% vs. 5.43%). Alpha diversity varies among groups, which are characterized by community state types including Lactobacillus-dominated communities in fertile females, an increase in diversity in all the other groups and Gardnerella-dominated communities occurring more often in ININF. While all single parameters did not allow predicting infections as the cause of infertility, including C. trachomatis IgG/IgA status together with 16S rRNA gene analysis of the ten most frequent taxa a total of 93.8% of the females were correctly classified. Further studies are needed to unravel the impact of the cervical microbiota in the pathogenesis of infectious infertility and its potential for identifying females at risk earlier in life.

COUP-TFI is an orphan nuclear receptor acting as a strong transcriptional regulator in different aspects of forebrain embryonic development. In this study, we investigated COUP-TFI expression and function in the mouse olfactory bulb (OB), a highly plastic telencephalic region in which continuous integration of newly generated inhibitory interneurons occurs throughout life. OB interneurons belong to different populations that originate from distinct progenitor lineages. Here, we show that COUP-TFI is highly expressed in tyrosine hydroxylase (TH)-positive dopaminergic interneurons in the adult OB glomerular layer (GL). We found that odour deprivation, which is known to downregulate TH expression in the OB, also downregulates COUP-TFI in dopaminergic cells, indicating a possible correlation between TH- and COUP-TFI-activity-dependent action. Moreover, we demonstrate that conditional inactivation of COUP-TFI in the EMX1 lineage results in a significant reduction of both TH and ZIF268 expression in the GL. Finally, lentiviral vector-mediated COUP-TFI deletion in adult-generated interneurons confirmed that COUP-TFI acts cell-autonomously in the control of TH and ZIF268 expression. These data indicate that COUP-TFI regulates TH expression in OB cells through an activity-dependent mechanism involving ZIF268 induction and strongly argue for a maintenance rather than establishment function of COUP-TFI in dopaminergic commitment. Our study reveals a previously unknown role for COUP-TFI in the adult brain as a key regulator in the control of sensory-dependent plasticity in olfactory dopaminergic neurons.

OBJECTIVE

There is a paucity of data for the assessment of frailty in acutely ill hospitalized older adults. We aim to (1) compare the performance of frailty measures [5-item scale of fatigue, resistance, ambulation, illnesses, and loss of weight) (FRAIL), Tilburg Frailty Indicator (TFI), and Clinical Frailty Scale (CFS)] in identifying frailty, using the widely adopted Frailty Index (FI) as "gold standard," and (2) compare their ability to predict negative outcomes among hospitalized older adults.

METHODS

Prospective cohort study.

METHODS

Acute inpatient care.

METHODS

A total of 210 patients (mean age 89.4 ± 4.6 years, 69.5% female) admitted to the Department of Geriatric Medicine.

METHODS

Premorbid frailty status was assessed by FI, FRAIL, TFI, and CFS. We collected data on comorbidities, severity of illness, functional status, and cognitive status. We compared area under receiver operator characteristic curves for FRAIL, TFI, and CFS against the reference FI. Multiple logistic regression was performed to examine the association between frailty and the primary outcome of in-hospital mortality.

RESULTS

Frailty prevalence estimates were 87.1% (FI), 50% (FRAIL), 80% (TFI), and 81% (CFS). Area under receiver operator characteristics against FI ranged from 0.81 [95% confidence interval (CI) 0.72-0.90: FRAIL] to 0.91 (95% CI 0.87-0.95: CFS), with no significant difference on receiver operating characteristic curve contrast. Frailty, as defined by FRAIL score ≥3, was associated with higher in-hospital mortality (6.7% vs 1.0%, P = .031) and length of hospitalization [10 days (6.0-17.5) vs 8 days (5.0-14.0), P = .043]. FI [odds ratio (OR) = 1.15, 95% CI 1.00-1.33, P = .05], FRAIL (OR = 3.31, 95% CI 1.43-7.67, P = .005), and CFS (OR = 2.57, 95% CI 1.14-5.83, P = .023) independently predicted in-hospital mortality adjusted for age, sex, and severity of illness.

CONCLUSIONS

FRAIL and CFS are simple frailty measures that may identify older adults at highest risk of adverse outcomes of hospitalization. FRAIL performed better in predicting in-hospital mortality.

This study aimed at comparing the Thylstrup-Fejerskov index (TFI) and the Dean's Index (DI) which were applied on three communities with different severity of dental fluorosis. A total of 1565 children aged between 11 and 18 yr with a mean age of 14.7 were examined for dental fluorosis with the TFI and 1155 of these children were also examined with the DI. The measurement error for the TFI was 0.50 (10 scale point) compared to 0.53 for DI (6 scale point). The Kappa values and the measurement-remeasurement correlation appeared to be better for the TFI. No difficulties were encountered in applying the TFI in contrast to the DI, which caused uncertainties in assessing the "questionable" and "very mild" scores, and this may explain the relatively better reproducibility of the TFI. The correspondence between both indices was determined. TFI 0 corresponded well with DI 0. The conversion values for TFI 1, 2, 3 and 4 into DI scores were 0.3, 0.8, 1.4 and 2.4 respectively. The TFI 5-9 corresponded with DI score 4. TFI could discriminate the severe forms of dental fluorosis which were categorized in Dean's highest score 4. TFI was able to reveal more dental fluorosis than DI in communities with minor and moderate dental fluorosis. In the community with severe dental fluorosis where more than 85% of all teeth exhibited a DI>> or = 1, both indices revealed a comparable prevalence of dental fluorosis. The TFI is considered a near ideal instrument.

OBJECTIVE

To examine the effects of dental fluorosis and total and self-etch bonding systems on microleakage of Class-V composite restorations in permanent molar teeth.

METHODS

Teeth were classified as three main groups according to Thylstrup-Fejerskov Index (TFI) as TFI=0, TFI=1-3 and TFI=4. Total and self-etching/bonding procedures were determined for each main group. Total-etching procedures were acid-etching for 30s and acid-etching for 60s with Single Bond/total-etch bonding system. Self-etching procedure was applied with Prompt-L-Pop/self-etch bonding system. 63 box-shaped Class-V cavities (4 x 2 x 2 mm) were prepared on mid-buccal/palatinal/lingual surfaces of teeth for totalling nine test groups (n=7). Restorations with composite material (Charisma) polymerized with halogen unit for 40s. Teeth were thermocycled between +5 degrees C - +55 degrees C (x500), immersed in 0.5% basic-fuchsin solution (37 degrees C, 24h) and separated longitudinally in bucco-lingual direction. Dye penetration was examined under stereomicroscope (3.2 x 10).

RESULTS

Microleakage levels were higher in teeth of TFI=4 than TFI=0 occlusally or cervically (P<.05). In TFI=0; total-etched teeth for 30s have statistically shown more leakage than total-etched teeth for 60s occlusally or cervically (P<.05). In TFI=4; microleakage levels were significantly higher for 30s than 60s cervically (P<.05). For all TFI levels, microleakage was commonly increased with self-etch system than total-etch system (P<.05). Generally, higher leakage was present at cervical margins than occlusal margins (P<.05).

CONCLUSIONS

Microleakage has increased by severity of dental fluorosis. Generally, more leakage was observed in total-etched teeth for 30s than 60s. Microleakage was commonly higher in self-etched teeth than total-etched teeth. More leakage was present at cervical margins than occlusal margins.

We aimed to evaluate the feasibility of transradial primary percutaneous coronary intervention (PCI) in patients with ST elevation myocardial infarction (STEMI) by comparing the procedural results and complications with those of transfemoral intervention. From April 1997 to October 2004, we enrolled 352 consecutive cases of STEMI who underwent primary PCI. The femoral route was used in 132 cases (TFI group) and the radial route was used in 220 cases (TRI group). Cases with Killips class IV, a negative Allen test or a non-palpable radial artery were excluded from our study. Baseline clinical and angiographic profiles were comparable in both groups. Vascular access time was 3.8 +/- 3.5 min in the TFI group and 3.6 +/- 3.1 min in the TRI group, and cath room to reperfusion time was 25 +/- 11 min in the TRI group and 26 +/- 13 min in the TRI group. The procedural success rate was 89% in the TFI group and 88% in the TRI group. Crossover occurred in 9 cases (4%) due to approaching vessel tortuosity in the TRI group. Major access site complications occurred in 7 cases (5%) in the TFI group, and there were no complications in the TRI group (p < 0.001). Although radial occlusion occurred in 5 cases of the TRI group, there was no evidence of hand ischemia. The total hospital stay was significantly shorter in TRI group than in TFI group. In conclusion, use of the radial artery might be a potential vascular access route in performing primary PCI in selected cases.

OBJECTIVE

To investigate the impact of PET and PET/CT scanning on decision-making in management planning and to identify the optimal setting for selecting candidates for surgery in suspicious recurrent ovarian cancer.

METHODS

A retrospective chart review was performed in patients with possible recurrent ovarian cancer after primary optimal cytoreduction and taxane/carboplatin chemotherapy who had undergone FDG PET or FDG PET/CT scans from July 2002 to August 2008 to help make treatment decisions. The analysis included 44 patients who had undergone a total of 89 PET scans. The positive PET scans were classified as follows. (1) localized (one or two localized sites of FDG uptake), (2) multiple (three or more sites of FDG uptake), (3) diffuse (extensive low-grade activity outlining serosal and peritoneal surfaces).

RESULTS

Of the 89 PET scans, 52 (58.4%) led to a change in management plan. The total number of patients in whom cytoreductive surgery was selected as the treatment of choice increased from 12 to 35. Miliary disseminated disease, which was not detected by PET scan, was found in 22.2% of those receiving surgery. Miliary disseminated disease was detected in 6 of the 12 patients with recurrent disease whose treatment-free interval (TFI) was <12 months, whereas none of those with a TFI of ≥12 months had such disease (P = 0.0031).

CONCLUSIONS

PET or PET/CT is useful for selecting candidates for cytoreductive surgery among patients with recurrent ovarian cancer. To avoid surgical attempts in those with miliary dissemination, patients with a TFI of ≥12 months are the best candidates for cytoreductive surgery.

Perioperative chemotherapy (CT) and chemoradiotherapy are widely used for advanced esophageal cancer. We evaluated the chemosensitivity of patients displaying recurrent esophageal cancer after esophagectomy with perioperative CT. From the database at National Cancer Center Hospital in Tokyo, we extracted recurrent esophageal cancer cases after perioperative CT and evaluated the effectiveness of the first CT against the recurrent disease according to the duration between termination of the original perioperative CT and recurrence with treatment-free intervals (<em>TFIs</em>) <or=6 and >6 months. Systemic CT for their recurrent disease was performed for 30 esophageal cancer patients after perioperative CT. All patients received 5-fluorouracil and cisplatin as perioperative CT, with relapses occurring at <em>TFIs</em> <or=6 months in 11 patients (eight received platinum-containing regimens and three received docetaxel for their recurrent disease) and >6 months in 19 patients (all received platinum-containing regimens). The response rate of patients experiencing a recurrence at <em>TFIs</em> <or=6 and >6 months was 0 and 37% (P = 0.029), the median progression-free survival was 2.8 and 4.8 months (log-rank P = 0.001) and the median overall survival was 6.1 and 10.2 months (log-rank P = 0.012), respectively. Recurrence at the <em>TFI</em> <or=6 months could represent resistance to CT, so regimens may need to be altered depending on a patient's specific <em>TFI</em>.

During a series of transfection experiments, the pRSV-luc plasmid used as an internal control was found to be sensitive to cotransfection with expression vectors for several members of the steroid/thyroid/retinoid superfamily of nuclear receptors. Therefore, a survey of the effect of these expression vectors on the activity of four reporter plasmids was conducted. In CV-1 cells, the activity of pRSV-luc, which contains the P. pyralis luciferase gene, was repressed by co-transfection of PPARalpha and ARP-1 and was activated by COUP-TFI. Expression of pSV40-luc, containing the same luciferase gene, was repressed by PPARalpha and HNF-4 and activated by both COUP-TFI and ARP-1. All four of these expression vectors reduced the expression of the pRL-TK plasmid, which contains the luciferase gene from Renilla reniformis. RXR expression vectors had no effect on luciferase activity in CV-1 cells but induced luciferase activity in H4IIEC3 hepatoma cells. This activation was blocked by the addition of ligand, 9-cis retinoic acid. pSV2-CAT, which contains the chloramphenicol acetyltransferase gene, was insensitive to all receptor expression vectors tested. Both the P. pyralis and R. reniformis luciferase genes appear to contain sequences that render them responsive to steroid/thyroid/retinoid nuclear receptors.

Isomers of retinoic acid are considered likely regulators of developmental pattern formation in vertebrate embryos. The orphan receptor COUP-TFI, which can alter cellular responses to retinoic acid in cultured cells, is expressed in distinct regions of the developing zebrafish and mouse anterior central nervous system. We asked if COUP-TFI can modulate retinoic acid signaling and anterior neural development in a vertebrate embryo by examining: (1) whether COUP-TFI could alter transcriptional responses to retinoic acid in Xenopus embryonic explants, and (2) whether misexpression of COUP-TFI could regulate anterior neural gene expression during early Xenopus development. The results from these studies show that COUP-TFI is a potent regulator of retinoic acid-induced gene expression in Xenopus embryonic cells, and that misexpression of COUP-TFI causes deficiencies in anterior neural structures and head development in Xenopus embryos with a concomitant change in anterior neural gene expression. These results support the proposition that COUP-TFI has a role in the elaboration and patterning of anterior neural gene expression in vertebrates, possibly via effects on the retinoic acid signaling pathways.

In vertebrates, the orphan nuclear receptors of the COUP-TF group function as negative transcriptional regulators that inhibit the hormonal induction of target genes mediated by classical members of the nuclear hormone superfamily, such as the retinoic acid receptors (RARs) or the thyroid hormone receptors (TRs). To investigate the evolutionary conservation of the roles of COUP-TF receptors as negative regulators in the retinoid and thyroid hormone pathways, we have characterized AmphiCOUP-TF, the homologue of COUP-TFI and COUP-TFII, in the chordate amphioxus (Branchiostoma floridae), the closest living invertebrate relative of the vertebrates. Electrophoretic mobility shift assays (EMSA) showed that AmphiCOUP-TF binds to a wide variety of response elements, as do its vertebrate homologues. Furthermore, AmphiCOUP-TF is a transcriptional repressor that strongly inhibits retinoic acid-mediated transactivation. In situ hybridizations revealed expression of AmphiCOUP-TF in the nerve cord of late larvae, in a region corresponding to hindbrain and probably anterior spinal cord. Although the amphioxus nerve cord appears unsegmented at the gross anatomical level, this pattern reflects segmentation at the cellular level with stripes of expressing cells occurring adjacent to the ends and the centers of each myotomal segment, which may include visceral motor neurons and somatic motor neurons respectively, among other cells. A comparison of the expression pattern of AmphiCOUP-TF with those of its vertebrate homologues, suggests that the roles of COUP-TF in patterning of the nerve cord evolved prior to the split between the amphioxus and vertebrate lineages. Furthermore, in vitro data also suggest that Amphi-COUP-TF acts as a negative regulator of signalling by other nuclear receptors such as RAR, TR or ER.

The crystal structure of NAD+-dependent DNA ligase from Thermus filiformis (Tfi) revealed that the protein comprised four structural domains. In order to investigate the biochemical activities of these domains, seven deletion mutants were constructed from the Tfi DNA ligase. The mutants Tfi-M1 (residues 1-581), Tfi-M2 (residues 1-448), Tfi-M3 (residues 1-403) and Tfi-M4 (residues 1-314) showed the same adenylation activity as that of wild-type. This result indicates that only the adenylation domain (domain 1) is essential for the formation of enzyme-AMP complex. It was found that the zinc finger and helix-hairpin-helix (HhH) motif domain (domain 3) and the oligomer binding (OB)-fold domain (domain 2) are important for the formation of enzyme-DNA complex. The mutant Tfi-M1 alone showed the activities for in vitro nick-closing and in vivo complementation in Escherichia coli as those of wild-type. These results indicate that the BRCT domain (domain 4) of Tfi DNA ligase is not essential for the enzyme activity. The enzymatic properties of Tfi-M1 mutant (deleted the BRCT domain) were slightly different from those of wild-type and the nick-closing activity of Tfi-M1 mutant was approximately 50% compared with that of wild-type.

OBJECTIVE

To evaluate the oral-health-related quality of life (OHRQoL) of children living in an endemic hydrofluorosis area.

METHODS

Schoolchildren aged 8-10 years living in an area with 3.38 ppm F water concentration completed a validated Spanish version of the Child Perceptions Questionnaire (CPQ(8-10ESP)). World Health Organization (WHO) criteria were applied for the diagnosis of dental caries and malocclusion. Additionally, the Thylstrup and Fejerskov Index (TFI) was used for fluorosis diagnosis. CPQ(8-10ESP) scores and oral health status were analyzed using non-parametric tests and logistic regression models.

RESULTS

Two hundred and twelve schoolchildren participated in this study. The mean CPQ(8-10ESP) score was 12.98 (SD 11.4). General oral health was rated as "poor" in 14.6%, "fair" in 41.5%, "good" in 25.9%, and "very good" in 17.9% of the children. Regarding overall well-being, half (51.6%) of the children perceived that the condition of their mouths disturbs their quality of life (QoL). Children with dental fluorosis (TF >4) had a high CPQ(8-10ESP) score in all domains (P < 0.005). Additionally, children with DMFS + dmfs >5 had higher scores in the oral symptoms, functional limitation, and emotional well-being CPQ(8-10ESP) domains (P < 0.05). Applying a CPQ(8-10ESP) cutoff point of 32, the OR values for severe malocclusion, caries, and fluorosis were 5.2 (P = 0.034), 4.6 (P = 0.006), and 5.1 (P = 0.007), respectively.

CONCLUSIONS

Malocclusion, caries, and fluorosis were associated with a negative impact on children's QoL.

In this paper, a new method for automatic sleep stage classification based on time-frequency image (TFI) of electroencephalogram (EEG) signals is proposed. Automatic classification of sleep stages is an important part for diagnosis and treatment of sleep disorders. The smoothed pseudo Wigner-Ville distribution (SPWVD) based time-frequency representation (TFR) of EEG signal has been used to obtain the time-frequency image (TFI). The segmentation of TFI has been performed based on the frequency-bands of the rhythms of EEG signals. The features derived from the histogram of segmented TFI have been used as an input feature set to multiclass least squares support vector machines (MC-LS-SVM) together with the radial basis function (RBF), Mexican hat wavelet, and Morlet wavelet kernel functions for automatic classification of sleep stages from EEG signals. The experimental results are presented to show the effectiveness of the proposed method for classification of sleep stages from EEG signals.