OBJECTIVE

To determine the relationship between the socioeconomic status and dental caries, gingivitis and fluorosis among Brazilian school children.

METHODS

One thousand students aged 12 from private and public schools were examined. The indexes used were DMFT or S (Decayed, Missing and Filled Teeth or Surfaces Index), BI (Bleeding Index), and TFI (Thylstrup and Feyerskov Index). The socioeconomic level was determined according family income and parents' educational level.

RESULTS

Parents' educational level data revealed a strong Pearson's correlation with income. No correlation was observed between dental caries prevalence, gingivitis and fluorosis and the studied social economic variables. The DMFT in private schools was 1.54+/-2.02, and in public schools was 2.48+/-2.51. BI was 14.7%+/-12.7% in private schools and 21.7%+/- 17.9% in public ones. The prevalence of fluorosis was 60.8% and 49.9%, respectively). These differences were statistically significant (p<0.05). Individuals with a larger number of decayed surfaces and the ones with a larger percent of bleeding surfaces were seen in public schools.

CONCLUSIONS

The socioeconomic level variables, income and parents' educational level, did not correlate with the events analyzed in the study. Other socioeconomic variables probably contributed to the observed differences between students from private and public schools.

OBJECTIVE

To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery.

METHODS

90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008.

RESULTS

Median age at time of surgery for bowel obstruction was 57 years (range, 26 to 85 years). All patients had received at least one line of platinum-based chemotherapy. Median time from diagnosis of primary disease to documented bowel obstruction requiring surgery was 19.5 months (range, 29 days-14 years). Median interval from date of completed course of chemotherapy preceding surgery for bowel obstruction was 3.8 months (range, 5 days-14 years). Ascites was present in 38/90(42%). 49/90(54%) underwent emergency surgery for bowel obstruction. The operative mortality and morbidity rates were 18% and 27%, respectively. Successful palliation, defined as adequate oral intake at least 60 days postoperative, was achieved in 59/90(66%). Only the absence of ascites was identified as a predictor for successful palliation (p=0.049). The median overall survival (OS) was 90.5 days (range, <1 day-6 years). Optimal debulking, treatment-free interval (TFI) and elective versus emergency surgery did not predict survival or successful palliation from surgery for bowel obstruction (p>0.05).

CONCLUSIONS

Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites.

The chicken ovalbumin upstream promoter transcription factors (COUP-TFs), members of the nuclear receptor superfamily, consist of two highly homologous subtypes, COUP-TFI (EAR-3, NR2F1) and COUP-TFII (ARP-1, NR2F2). They are referred to as orphan receptors because the COUP-TF ligands have yet to be identified. Since the discovery of COUP-TFs in 1986, extensive studies have demonstrated their crucial functions in a variety of developmental processes, such as organogenesis, angiogenesis, and metabolic homeostasis. Recently, emerging evidence has highlighted that COUP-TFs, specifically COUP-TFII, play important roles in tumorigenesis. In this review, we will discuss the critical functions of COUP-TFII in the development of the tumor microenvironment, the progression of various cancers, and its underlying mechanisms.

Retinoic acid (RA) is a positive regulator of P19 cell differentiation. Silencing of pre-B cell leukemia transcription factors (PBXs) expression in P19 cells (AS cells) results in a failure of these cells to differentiate to endodermal cells upon RA treatment. Chicken Ovalbumin Upstream Promoter Transcription Factor I (COUP-TFI) is an orphan member of the steroid-thyroid hormone superfamily. RA treatment of wild type P19 cells results in a dramatic increase in the expression of COUP-TFI; however, COUP-TFI mRNA levels fail to be elevated upon RA treatment of AS cells indicating that PBX expression is required for elevation in COUP-TFI expression. To study the role of COUP-TFI during RA-dependent differentiation of P19 cells, AS cells that inducibly express various levels of COUP-TFI were prepared. Exogenous expression of COUP-TFI in AS cells, in a dose-dependent fashion, leads to growth inhibition, modest cell cycle disruption, and early apoptosis. Furthermore, AS cells can overcome the blockage in RA-dependent differentiation to endodermal cells when either pharmacological levels of COUP-TFI are expressed or a combination of both the expression of physiological levels of COUP-TFI and RA treatment. Additionally, the mRNA level of several pluripotency associated genes including OCT-4, DAX-1, and SF-1 in the COUP-TFI expressing AS cells are reduced. Moreover, analysis of the expression of primary RA response genes indicates that COUP-TFI is involved in the regulatory modulation of the expression of at least two genes, CYP26A1 and HoxA1. These studies demonstrate that COUP-TFI functions as a physiologically relevant regulator during RA-mediated endodermal differentiation of P19 cells.

Increased aspirin resistance may contribute to the increase in thrombotic events observed in patients with type 2 diabetes. In this study, we examined if acute exposure to increased plasma glucose impaired the inhibitory effects of aspirin on platelet activation. Whole-blood samples were incubated with 100 (euglycemia), 200, 300, and 600 mg/dl glucose followed by incubation with aspirin [acetylsalicylic acid (ASA)]. Using flow cytometry, GPIIb-IIIa and P-selectin were analyzed in unstimulated and arachidonic acid (AA)-stimulated platelets. In euglycemic blood, AA caused a significant increase in platelet GPIIb-IIIa expression [unstimulated: 59.5+/-8.2 total fluorescence intensity (TFI), AA stimulated: 319.6+/-42.7 TFI, P=.002] and P-selectin (4.4+/-0.7 and 179.5+/-38.5 TFI, P<.001). In vitro, ASA significantly inhibited both GPIIb-IIIa expression (36.5%) and P-selectin expression (81%; P<.005). However, increased blood glucose (200 mg/dl) significantly impaired the inhibitory effect of ASA (84% for GPIIb-IIIa, P<.005; 48% for P-selectin, P=NS). Increasing glucose to 600 mg/dl completely overwhelmed the inhibitory effect of ASA. A statistically significant interaction between glucose concentration and ASA dose was found (P<.001 for GPIIb-IIIa and P=.004 for P-selectin). In vitro, concentration-dependent stress hyperglycemia significantly impaired the inhibitory effects of aspirin on human platelet GPIIb-IIIa and P-selectin expression. Under acute hyperglycemic conditions, the effectiveness of ASA to inhibit platelets via the AA-activation pathway may be significantly reduced.

Elevated level of fluoride (F(-)) in drinking water is a well-recognized risk factor of dental fluorosis (DF). While considering optimization of region-specific standards for F(-), it is reasonable, however, to consider how local diet, water sourcing practices, and non-F(-) elements in water may be related to health outcomes. In this study, we hypothesized that non-F(-) elements in groundwater and lifestyle and demographic characteristics may be independent predictors or modifiers of the effects of F(-) on teeth. Dental examinations were conducted among 1094 inhabitants from 399 randomly-selected households of 20 rural communities of the Ziway-Shala lake basin of the Main Ethiopian Rift. DF severity was evaluated using the Thylstrup-Fejerskov Index (TFI). Household surveys were performed and water samples were collected from community water sources. To consider interrelations between the teeth within individual (in terms of DF severity) and between F(-) and non-F(-) elements in groundwater, the statistical methods of regression analysis, mixed models, and principal component analysis were used. About 90% of study participants consumed water from wells with F(-) levels above the WHO recommended standard of 1.5mg/l. More than 62% of the study population had DF. F(-) levels were a major factor associated with DF. Age, sex, and milk consumption (both cow's and breastfed) were also statistically significantly (p<0.05) associated with DF severity; these associations appear both independently and as modifiers of those identified between F(-) concentration and DF severity. Among 35 examined elements in groundwater, Ca, Al, Cu, and Rb were found to be significantly correlated with dental health outcomes among the residents exposed to water with excessive F(-) concentrations. Quantitative estimates obtained in our study can be used to explore new water treatment strategies, water safety and quality regulations, and lifestyle recommendations which may be more appropriate for this highly populated region.

BACKGROUND

Treatment with docetaxel in combination with prednisone is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). For patients failing first-line docetaxel no standard has emerged.

OBJECTIVE

The outcome in routine daily clinical practice of a cohort of unselected chemotherapy-naïve mCRPC patients treated with docetaxel plus methylprednisolone as first- and further-line treatment in a single institution was investigated.

METHODS

Data from the medical records of patients treated with docetaxel plus methylprednisolone either in a three-weekly (75 mg/m(2)) (D3) or a three-of-four-weekly (35 mg/m(2))(D1) schedule as first- or further-line treatment were analysed with respect to clinical and prostate-specific antigen (PSA) response, time-on-treatment (TOT), treatment-free interval (TFI), overall survival time (OS) and toxicity and were compared to the results of the registration study TAX 327.

RESULTS

Out of 41 patients, 28 and 13 received first-line docetaxel according to the D3 and the D1 schedules respectively. An overall PSA response ≥50% was achieved in thirty patients (73%). In ten patients (24%) the PSA level was normalised. The median OS of the total population was 18.7 months. No significant differences were observed between the D3 and the D1 regimens with respect to PSA response, duration of PSA response, TOT, TFI and OS. Patients obtaining a normalisation of PSA level achieved a significantly superior OS, TOT and TFI compared to those without normalisation of PSA. Second-line treatment with docetaxel in nine patients induced a normalisation in PSA level in two (22%). The TOT and TFI from the start of second-line treatment, was significantly superior in docetaxel compared to non-docetaxel treated patients. Treatment with docetaxel was well-tolerated and only two patients were withdrawn for non-haematological toxicity during first- and further-line treatment. There were no differences in either subjective or objective side-effects between both treatment schedules.

CONCLUSIONS

The results of the retrospective analysis of non-selected patients with mCRPC treated with docetaxel chemotherapy are in line with the data from TAX 327. Normalisation of PSA during first-line treatment with docetaxel is associated with a better survival irrespective of second- or further-line treatment used. Retreatment with docetaxel in second- or further-line remains a treatment option in docetaxel-sensitive patients.

OBJECTIVE

A previously reported phase 2 trial suggested substantial clinical activity associated with the combination of a platinum agent and tamoxifen in the treatment of platinum-resistant ovarian cancer. We wished to confirm or refute this observation in a patient population with well-characterized platinum-resistant disease.

METHODS

Patients with ovarian or fallopian tube cancers or primary carcinoma of the peritoneum whose disease had either failed to respond to a platinum-based regimen or had responded but experienced a "treatment-free interval (TFI)" of < or =3 months, or if the TFI was >3 months they had been retreated and failed a platinum-based program, were eligible for entry into this phase 2 single institution protocol. Carboplatin (AUC 5) was delivered on a q-21 day cycle. Tamoxifen was administered at a dose of 80 mg/day for the first cycle, and then reduced to 40 mg/day. Treatment was to be continued until evidence of disease progression or unacceptable toxicity.

RESULTS

Fourteen patients were treated on this phase 2 trial. In addition to being platinum-resistant, 10 patients had cancers that were also documented to be taxane-resistant (similar criteria to that defined above for platinum). While treatment was generally well tolerated, there were no objective (measurable disease or CA-125 response criteria) or subjective responses to this treatment program.

CONCLUSIONS

In this phase 2 trial, we have been unable to confirm a meaningful level of clinical activity for the combination of carboplatin plus tamoxifen in a patient population with well-characterized platinum-resistant ovarian cancer.

OBJECTIVE

Treatment of epithelial ovarian cancer patients relapsing with a short treatment-free interval (TFI) after prior chemotherapy is unsatisfactory. This phase II trial evaluated the activity and feasibility of pegylated liposomal doxorubicin (PLD) plus gemcitabine in this setting.

METHODS

Patients who had received prior platinum and paclitaxel with a TFI 0-12 months received PLD 25 mg/m(2)day 1 plus gemcitabine 800 mg/m(2)day 1, 8 every 21 days. Gemcitabine was dose escalated to 1000 mg/m(2)day 1, 8 from course 2 in the absence of grade 3/4 toxicity. The primary endpoint was progression-free survival (PFS). Patients were stratified according to response to primary chemotherapy.

RESULTS

Seventy-nine patients (n=26 with CR on prior chemotherapy and TFI 6-12 months; n=20 with CR and TFI 0-6 months; n=33 with PR/SD and TFI 0-12 months) were enrolled. The median age was 59 years (range 31-77 years), and 33 patients had received ≥ 2 prior treatments. A median of five courses was delivered per patient (total 389 courses). Gemcitabine was dose escalated in 124 courses and reduced in 105 courses. No PLD dose reductions occurred. Grade 3/4 toxicities were febrile neutropenia (n=4), PPE (n=2), and mucositis (n=2). One toxic death occurred (pneumonitis/alveolitis). Responses were complete in 5.1%, partial in 27.9%, and stable disease in 55.7%. Median OS and PFS were 12.5 and 6.4 months, respectively.

CONCLUSIONS

The PLD-gemcitabine combination is an effective and well-tolerated salvage treatment for relapsed epithelial ovarian cancer and is a valid candidate for evaluation in a phase III trial.

OBJECTIVE

The platinum-free interval (PFI) is an important entity in the treatment of women with epithelial ovarian cancer. The purpose of this study was to determine on clinical samples whether a taxane-free interval (TFI), as defined by in vitro extreme drug resistance assay, existed in women previously exposed to platinum and taxane chemotherapy.

METHODS

Records were examined from 2003 to 2006 to find all patients with epithelial ovarian cancer who had previous exposure to platinum and taxane therapy. Further examination was done to find all patients who underwent secondary cytoreduction and had their tumor submitted for extreme drug resistance assay.

RESULTS

Thirty-four women meeting the above criteria were found. The mean PFI was 25 months (median 18). The mean TFI was 27 months (median 20). Over 44% of the patients have been exposed to more than just a course of platinum and a course of a taxane. In patients having a PFI of>>or=12 months, 38.8% had extreme drug resistance (EDR) to carboplatin and 41.9% EDR to cisplatin. Conversely, in patients having a TFI of>>or=12 months, 89.7% had EDR to paclitaxel and 82.8% EDR to docetaxel.

CONCLUSIONS

While only a small percentage have EDR to carboplatin and cisplatin after a PFI of>>or=12 months, almost 90% of patients with a TFI)or=12 months showed EDR to paclitaxel in vitro.

OBJECTIVE

To undertake a blind caries and fluorosis prevalence study of Grade 1 (aged 5/6 yr) and Grade 4-7 (aged 8-12 yr) children from naturally water-fluoridated (1 ppm, since 1985) Burghead, Findhorn & Kinloss (F), and nearby nonfluoridated Buckie & Portessie (N-F), in rural Morayshire, Scotland.

METHODS

A blind clinical (+ 10% repeats) caries study of the above townships' 5/6-yr-old lifetime (15 F; 43 N-F), and 8-12-yr-old lifetime (55 F; 136 N-F)/school-lifetime (31 F; 37 N-F) residents was undertaken following bussing of these children to a common examination site in close-by Elgin Town Hall. Initially, each child was asked about their own perception of the aesthetics of their maxillary front teeth. Fluorosis was assessed clinically using the TF Index, as well as photographically - for later blind scoring (+ 10% repeats for lifetime 8-12-yr-olds) of slides by four dental and two lay 'jurors', alongside a now-established UK 'bench-mark' mildly mottled (TFI = 2), fluorosis comparator slide, judged in previous studies to be aesthetically lay-acceptable. In addition, by parental questionnaire, information was sought concerning their child's fluoride supplement and dentifrice usage histories.

RESULTS

For 5/6-yr-olds, mean primary caries scores were 96.0% less in fluoridated than nonfluoridated subjects (P < 0.01). In 8-12-yr-olds, DMFT values favoured water-fluoridated subjects; their caries-free trend was significant (P < 0.001 overall). Clinically, 33% of all lifetime F subjects and 18% of all N-F pupils had fluorosed maxillary anterior teeth (P = 0.045), but no statistically significant difference was found between the 7% F and 3% N-F subjects with TFI scores>> 2 (P = 0.25). Photographically, 'jury' mottling assessment (+ 10% repeats) of projected slides resulted in at least 1 : 6 positive scores in 43.6% of F and 30.9% of N-F pupils, albeit they unanimously scored only nine F and five N-F children as having fluorosed teeth (P < 0.01). In no case did all members score TFI>> 2. Dental and lay scorers rated TFI = (1/2) in only a further 9.1% and 5.5% of F subjects, respectively, compared to 0.7% and 1.5% respectively of N-F pupils. Again, TFI>> 2 was scored unanimously in no child. No differences were found regarding the children's own degree of anterior tooth aesthetic nonacceptability between F (11%) and N-F (12%) prevalence (P = 0.75). Finally, only one F child had taken F supplements and, while 26 N-F had used F drops, no significant relationship was found between their usage and TFI values in the latter group (P = 0.49). Additionally, no relationship was noted between clinical TFI scores and the age at which parents stated fluoridated dentifrice toothbrushing commenced, between 0 and 24 + months of age.

CONCLUSIONS

Considerable caries benefit has accrued to those Morayshire rural children who have received naturally fluoridated water (at 1 ppm) throughout their lives, as compared to their socioeconomically similar, nonfluoridated rural counterparts. Furthermore, in spite of all but two subjects claiming to have brushed regularly with fluoridated dentifrice (and no evidence of the availability of nonfluoridated toothpaste being purchasable in the five townships), only borderline mild fluorosis disadvantages have been noted clinically, and none by the subjects' own aesthetic perceptions. Finally, no evidence was found to suggest any delay in permanent tooth eruption patterns of the F subjects. It would seem appropriate therefore, that adjustment of Scots' drinking waters' natural fluoride levels to 1 ppm should be pursued to extend similar dental advantages to the vast majority of that population (both young and old) which, it is well documented, has the worst dental health of mainland UK.

Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) play a critical role in initiating and accelerating atherosclerosis. This study evaluated the imaging properties of (99m)Tc-TNFR2-Fc-IL-1RA ((99m)Tc-TFI), a dual-domain cytokine radioligand that targets TNF-α and IL-1β pathways, in assessing atherosclerosis development in apolipoprotein-E-deficient (ApoE(-)(/)(-)) mice.

METHODS

The feasibility and specificity of detecting atherosclerosis with (99m)Tc-TFI SPECT imaging were investigated in ApoE(-)(/)(-) and ApoE(+)(/)(+) mice. Fifty-four ApoE(-)(/)(-) mice were fed either an atherogenic diet (AGD) or a normal diet (ND) beginning at 5 weeks of age. Eighteen Apo-E wild-type (ApoE(+)(/)(+)) mice were fed an ND. Two groups of ApoE(-)(/)(-) mice (n=12 each group) on AGD and ND were imaged three times with (99m)Tc-TFI and a high-resolution SPECT system at 20-25, 30-40, and 48-52 weeks to study the evolution of atherosclerotic plaque.

RESULTS

Focal radioactive accumulations in the aortic arch region were observed in the ApoE(-)(/)(-) mice (n=12) on AGD but not in the ApoE(+)(/)(+) mice on ND (n=10). Apo-E(-)(/)(-) mice on ND (n=11) exhibited lower radioactive uptake than ApoE(-)(/)(-) mice on AGD (P<0.05). Co-injection of an excess of cold ligand with (99m)Tc-TFI resulted in significant reduction of (99m)Tc-TFI uptake in the ApoE(-)(/)(-) mice on AGD. Longitudinal studies showed that (99m)Tc-TFI uptake in the aortas of ApoE(-)(/)(-) mice progressively increased from 20 to 48 weeks. Real-time PCR assays demonstrated that atherosclerotic aortas expressed significantly higher IL-1β and TNF-α than the aortas from wild-type controls.

CONCLUSIONS

Atherosclerotic plaques were detected by (99m)Tc-TFI imaging in ApoE(-)(/)(-) mice. (99m)Tc-TFI is promising for specific detection of inflammatory response in atherosclerotic plaques.

Serum 'free thyroxine' was measured as a thyroid function index (TFI) in 238 women with early breast cancer and 107 normal controls. The mean TFI was significantly lower in the cases compared with controls. The TFI was not related to pathological stage but correlated with histological grade, with the highest values found in well-differentiated (grade I) and the lowest in anaplastic tumours (grade III). A similar result was obtained with the urinary and androsterone:aetiocholanolone (5 alpha:5 beta) ratio in that the ratio was significantly lower in patients with grade III than in those with grade I tumours. These results indicate that thyroid hormones may be involved in tumour cell differentiation. Patients with low 5 alpha/5 beta ratios had significantly faster recurrence rates than those with high ratios. A similar trend was found for the TFI. The TFI decreases after mastectomy and at 12 months after operation is still below the pre-operative basal level.

OBJECTIVE

The phase 3 MONALEESA-2 study demonstrated that addition of ribociclib (RIB) to letrozole (LET) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Here, we evaluated duration of response (DoR), tumor shrinkage, PFS by treatment-free interval (TFI), and health-related quality of life (HRQoL).

METHODS

Postmenopausal women (N = 668) with HR+ , HER2- ABC and no prior systemic therapy for ABC were randomized to RIB (600 mg/day; 3 weeks on/1 week off) plus LET (2.5 mg/day; continuous) or placebo (PBO) plus LET. Primary end point was PFS; HRQoL was the secondary end point; DoR was exploratory end point and PFS by TFI was post hoc analysis.

RESULTS

Of 501 pts with measurable disease and confirmed complete or partial response, median DoR was 26.7 months (95% CI, 24.0-NR) in the RIB arm versus 18.6 months (95% CI, 14.8-23.1) in the PBO arm. At 8 weeks, more pts in the RIB arm (32%) versus the PBO arm (17%) experienced best percentage change ≥ 60%. The average pain reduction was greater in the RIB arm (26%) versus the PBO arm (15%). PFS benefit was seen with RIB vs PBO, irrespective of TFI.

CONCLUSIONS

RIB plus LET versus PBO plus LET is associated with earlier and more durable tumor response, greater degree of tumor shrinkage and pain reduction, and PFS benefit irrespective of TFI. These data further support RIB plus LET as a first-line treatment option for postmenopausal women with HR+ , HER2- ABC.

Our recent experience indicates that the desmoplastic variant of tumor of the follicular infundibulum (TFI) is not, as previously believed, entirely uncommon. To clarify the defining clinical and microscopic features of TFI with special relevance to the histologic variants, we retrospectively reviewed cases with a histologic diagnosis of TFI between 1999 and 2008. Of the 74 cases retrieved, 53 TFI cases in 50 patients were identified with an incidence approximating 17 per 100,000. Clinically, TFI seems to be slightly more common in men (52% vs. 48%) and more common on the head and neck (around 77%) and presents as plaques (approximately 47%) and as multiple lesions (6%). Histologically, the majority showed classic features of a horizontal plate-like proliferation of large, bland-appearing, pale epithelial cells. Other features included an eosinophilic cuticle (70%), ductal differentiation (45%), cornoid lamellae (17%), and desmoplasia (11%). Of interest, approximately one fourth (25%) were associated with other cutaneous lesions, which included basal cell carcinoma, actinic keratosis, desmoplastic malignant melanoma, junctional melanocytic nevus, tricholemmoma, and epidermal inclusion cyst. In addition to expanding the constellation of the clinical and histopathologic findings, the increased association with other cutaneous lesions in the current study suggests that TFI may represent an epidermal reaction pattern.

BACKGROUND

Chlamydia trachomatis is the most reported bacterial sexually transmitted disease, especially among young women worldwide. The aim of this study was comparison the prevalence of Chlamydia trachomatis infection in woman with tubal infertility by means of PCR and cell culture techniques.

METHODS

Fifty-one women with confirmed TFI were enrolled in this study in (avicenna infertility Clinic) between January 2010 and January 2011. Cervical swab and cytobrush specimens were collected from each patient by gynecologists and sent to laboratory in transport media. Detection of Chlamydia trachomatis in samples was performed using PCR and bacteria culture in MacCoy cell line. The data were analyzed by Fisher's exact test and independent t-test. Statistical significance was established at a p-value <0.05.

RESULTS

A significant relation was observed between increased the age of first intercourse and chlamydial infection. Six (11.7%) samples had positive PCR result, whereas cell culture results were positive in only 2 (3.9%) samples. A significant relation was also identified between the duration of infertility and infection (p < 0.05) by PCR versus cell culture method.

CONCLUSIONS

The results showed that PCR is a rapid method, compared to cell culture for detecting Chlamydial organism. It also became clear that the age at first intercourse is important to predict the likelihood of Chlamydia trachomatis.

The objective of the present study was to evaluate the clinical usefulness of the simultaneous measurement of three serological markers of chlamydial infection in women with tubal factor infertility (TFI) and spontaneous miscarriage. Serum was collected from 87 patients (33 with TFI and 54 with spontaneous miscarriage) and analyzed for the presence of IgG and IgA antibodies against Chlamydia trachomatis MOMP antigen (Dia.Pro) and IgG antibodies to chlamydial heat shock protein 60 (cHSP60) antigen (Medac). We determined a high degree (64.5 %) of seropositivity against chlamydial antigens in our study population. The prevalence of persistent chlamydial infection has tended to be higher in the group of patients with TFI (41.4 %) than in patients with spontaneous miscarriage (21.3 %). The serum level of IgA, as a marker of active infection, was statistically higher in the TFI group with persistent infection than in the corresponding spontaneous miscarriage group (p = 0.008), while the serum level of IgG showed no statistically significant differences compared with the spontaneous miscarriage group with persistent infection (p = 0.227). Also, using the receiver operating characteristic (ROC) curve, we found that the serum level of IgA has the ability to discriminate patients with persistent chlamydial infection between the TFI and miscarriage groups, with a sensitivity and specificity of 74.3 % and 71.4 %, respectively. To the best of our knowledge, the present study is the first study which, besides the already confirmed linkage between serologic evidence of persistent chlamydial infection and TFI, also confirmed associations between spontaneous miscarriage and serologic evidence of persistent chlamydial infection.

BACKGROUND

This study aimed to determine whether medical history, transvaginal ultrasound (TVU) or Chlamydia trachomatis antibody testing (CAT), alone or in combination, could provide a non-invasive, clinically useful screening test for predicting tubal factor infertility (TFI) in subfertile women.

METHODS

Prior to tubal evaluation, relevant medical history, TVU findings, and enzyme-linked immunosorbent assay (ELISA) IgG CAT results were collected. Sensitivity, specificity, likelihood ratios (LR) and accuracy for predicting TFI, as determined by laparoscopy and dye hydrotubation, were calculated for each test alone, and in parallel and series combination.

RESULTS

Thirty per cent (63/207) were diagnosed with TFI. The highest sensitivity (67%, 95% CI: 54-77) included any positive test, yet missed one in three women with TFI. The highest specificity (100%, 95% CI: 97-100) required all three tests positive, but identified only three women. Only the combination of CAT and TVU rated as a good clinical test, but confidence intervals were wide due to the small numbers affected. The combination of CAT or TVU and CAT alone reported the highest accuracy (73%, 95% CI: 66-78), misdiagnosing one in four women.

CONCLUSIONS

Medical history, TVU appearances, and ELISA IgG CAT alone, or in combination, failed to predict accurately TFI in subfertile women.

The purpose of the present study was to determine the effect of metacognitive therapy (MCT) on symptoms of body dysmorphic disorder (BDD) and on symptoms of thought-fusion, by means of a wait-list controlled clinical trial. Participants were referred from dermatology and cosmetic surgery clinics in the city of Isfahan, Iran, and 20 patients were selected on the basis of DSM-IV-TR diagnostic criteria for BDD. They were randomly assigned to either the experimental or the wait-list control group. The Yale-Brown Obsessive Compulsive Scale Modified for Body Dysmorphic Disorder (BDD-YBOCS) and the Thought-Fusion Inventory (TFI) were used as the outcome measures. The experimental group received 8 weekly metacognitive intervention sessions. The control group was in the waiting-list until the end of the follow-up. Measures were taken at pre-test, post-test (after 2 months) and follow-up (after 6-months). The results of analysis of variance showed that MCT significantly reduced the symptoms of BDD and of thought-fusion, compared to the wait-list. Effects on both outcome measures were maintained at 6-months follow-up.

OBJECTIVE

The objective of our laboratory study was to determine the bonding efficacy of two-step self-etching primer system (Clearfil SE Bond), all-in-one adhesive (Clearfil Tri S Bond) and acid-etching system (Single Bond) to human fluorosed dentine.

METHODS

Forty-eight human molars were grouped according to modified Thylstrup-Fejerskov index (TFI) into normal (N, TFI 0), mild fluorosis (ML, TFI 1-3) and moderate fluorosis (MD, TFI 4-6). Superficial dentine was exposed and ground with 600-grit silicon carbide paper. Teeth of each group were randomly divided into three sub-groups. Each sub-group was treated with one of the three bonding systems. A resin composite was built up on the bonded surfaces and stored in water at 37 degrees C for 24h. They were serially sectioned in buccal-lingual direction into 0.7-1.0mm thick slabs. Slices were trimmed for microtensile bond test and stressed in tension at a crosshead speed of 1mm/min. The data were analyzed with two-way ANOVA (p=0.05). The adhesive/dentine interfaces of the bonded specimens were examined by a FE-SEM.

RESULTS

Significantly higher microtensile bond strength (microTBS) was found with Clearfil SE Bond to mild fluorosed dentine than did Single Bond and Clearfil Tri S Bond. Lower microTBS were found for Single Bond (not significant) and Clearfil Tri S Bond than Clearfil SE Bond with moderately fluorosed dentine. Thickness of the hybrid layer produced by Clearfil SE Bond in mild and moderately fluorosed groups was less than with normal dentine.

CONCLUSIONS

Two-step self-etching system, Clearfil SE Bond, showed a higher bonding performance to fluorosed dentine than Single Bond and Tri S Bond.

BACKGROUND

Contradictory results have been reported for transcranial direct current stimulation (tDCS) as treatment for tinnitus. The recently developed high-definition tDCS (HD tDCS) uses smaller electrodes to limit the excitation to the desired brain areas.

OBJECTIVE

The current study consisted of a retrospective part and a prospective part, aiming to compare 2 tDCS electrode placements and to explore effects of HD tDCS by matched pairs analyses.

METHODS

Two groups of 39 patients received tDCS of the dorsolateral prefrontal cortex (DLPFC) or tDCS of the right supraorbital-left temporal area (RSO-LTA). Therapeutic effects were assessed with the tinnitus functional index (TFI), a visual analogue scale (VAS) for tinnitus loudness, and the hyperacusis questionnaire (HQ) filled out at 3 visits: pretherapy, posttherapy, and follow-up. With a new group of patients and in a similar way, the effects of HD tDCS of the right DLPFC were assessed, with the tinnitus questionnaire (TQ) and the hospital anxiety and depression scale (HADS) added.

RESULTS

TFI total scores improved significantly after both tDCS and HD tDCS (DLPFC: P < .01; RSO-LTA: P < .01; HD tDCS: P = .05). In 32% of the patients, we observed a clinically significant improvement in TFI. The 2 tDCS groups and the HD tDCS group showed no differences on the evolution of outcomes over time (TFI: P = .16; HQ: P = .85; VAS: P = .20).

CONCLUSIONS

TDCS and HD tDCS resulted in a clinically significant improvement in TFI in 32% of the patients, with the 3 stimulation positions having similar results. Future research should focus on long-term effects of electrical stimulation.

The formation of functional cortical maps in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. To understand how transcriptional regulation influences network activity and neuronal excitability within the neocortex, we used mice deficient for Nr2f1 (also known as COUP-TFI), a key determinant of primary somatosensory (S1) area specification during development. We found that the cortical loss of Nr2f1 impacts on spontaneous network activity and synchronization of S1 cortex at perinatal stages. In addition, we observed alterations in the intrinsic excitability and morphological features of layer V pyramidal neurons. Accordingly, we identified distinct voltage-gated ion channels regulated by Nr2f1 that might directly influence intrinsic bioelectrical properties during critical time windows of S1 cortex specification. Altogether, our data suggest a tight link between Nr2f1 and neuronal excitability in the developmental sequence that ultimately sculpts the emergence of cortical network activity within the immature neocortex.

Keywords: Nr2f1/COUP-TFI; intrinsic excitability; layer V pyramidal neurons; somatosensory cortex; spontaneous activity.

Traditional response criteria may be insufficient to characterize full clinical benefits of anticancer immunotherapies. Consequently, endpoints such as durable response rate (DRR; a continuous response [complete or partial objective response] beginning within 12 months of treatment and lasting ≥6 months) have been employed. There has not, however, been validation that DRR correlates with other more traditional endpoints of clinical benefit such as overall survival.

We evaluated whether DRR was associated with clinically meaningful measures of benefit (eg, overall survival [OS], quality of life [QoL], or treatment-free interval [TFI]) in a phase 3 clinical trial of an oncolytic virus for melanoma treatment. To evaluate the association between DRR and OS and to mitigate lead time bias, landmark analyses were used. QoL was evaluated using the FACT-BRM questionnaire (comprising the FACT-BRM Physical, Social/Family, Emotional, and Functional well-being domains, the Additional Concerns, Physical and Mental treatment-specific subscales, and the Trial Outcome Index [TOI]). TFI was defined as time from the last study therapy dose to first subsequent therapy dose (including any systemic anticancer therapy for melanoma after study therapy discontinuation).

Four hundred thirty-six patients were included in the intent-to-treat population. Achieving DR was associated with a statistically significant improvement in OS in a landmark analysis at 9 months (HR = 0.07; P = 0.0003), 12 months (HR = 0.05, P < 0.0001), and 18 months (HR = 0.11; P = 0.0002) that persisted after adjusting for disease stage and line of therapy. Achieving a DR was associated with a longer median TFI (HR = 0.33; P = 0.0007) and a higher TOI improvement rate (58.1% versus 30.0%; P = 0.025).

Achieving a DR was associated with clinical benefits such as improved OS and QoL and prolonged TFI, thus supporting the usefulness of DR as a meaningful immunotherapy clinical trial endpoint.

ClinicalTrials.gov identifier, NCT00769704 ( https://clinicaltrials.gov/ct2/show/NCT00769704 ) October 7, 2008.

The aim of this study was to identify factors that might explain the similar level of prevalence and severity of dental fluorosis in two neighboring areas in Tanzania: Kibosho; 0.2 mg fluoride/l, n = 96 and Arusha; 3.6 mg fluoride/l in drinking water, n = 80. Subjects aged 8-16 years were examined for dental fluorosis using the Thylstrup and Fejerskov Index (TFI). Based on the score on the upper left central incisor, the prevalence was not significantly different between the communities (TFI>> or = 1). The severity, however, was significantly higher in Arusha. The areas had different food habits, e.g., type of weaning food used, and the use of magadi, a fluoride containing salt. In Arusha, 99% of the children had been given lishe, which is a magadi-free weaning food. Conversely in Kibosho, 61% used lishe while 39% used the magadi-containing weaning food kiborou. Magadi was used as food tenderizer in 'adult food' by 98% in Kibosho and 45% in Arusha. Residential area and use of magadi explained 5% of the variance in TFI scores in inter-area analyses. In intra-area analyses, weaning food in Kibosho and use of magadi in Arusha had a significant effect, but the total explained variance was only 5 and 4%, respectively. Apart from fluoride in the drinking water, other sources of fluoride such as use of magadi in weaning food (kiborou) and in the adult food may partly explain the high prevalence and severity of dental fluorosis in the community with 0.2 mg fluoride per liter in the drinking water.