OBJECTIVE

The present study aimed to examine the efficacy of metacognitive therapy in treatment of patients with pure obsession.

METHODS

Six patients suffering from pure obsession were selected using purposeful sampling method and were included after meeting the inclusion criteria of the study. Patients were assessed using the structured clinical interview for DSM- IV Axis I disorder - patient edition (SCID- I/P). The patients' main obsessions were present including sexual, aggressive and blasphemous thoughts. In response to these obsessions, all patients used covert rituals and compulsive behaviors. In this study, multiple baseline, a major type of single- subject empirical design, was employed. During the baseline (3-7 weeks) and treatment (14 weekly sessions) and follow-up (3 months) patients filled out the Obsessive Compulsive Inventory (Revised form) (OCI-R), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Metacognitive Questionnaire (MCQ), Thought Fusion Inventory (TFI) and Beck Depression Inventory- II (BDI-II). To implement metacognitive therapy, Well's theraputicimstruction for OCD was used.

RESULTS

The results indicated that Metacognitive Therapy (MCT) is effective in reducing obsessive - compulsive symptoms and in modifying metacognitive beliefs and thought-fusion beliefs.

CONCLUSIONS

Metacognitive therapy is effective in treatment of pure obsession.

OBJECTIVE

The purpose of this study was to compare the prevalence and severity of dental fluorosis among vegetarian and nonvegetarian children and adolescents living in an area where dental fluorosis is endemic.

METHODS

An analytical cross-sectional retrospective study.

METHODS

Children (n = 165) aged 6-18 years, from five schools in Arusha town were examined. The children had a life-long exposure to drinking water with 3.6 mg F/litre. The severity of dental fluorosis was assessed using the Thylstrup & Fejerskov Index (TFI).

RESULTS

In the vegetarian group (n = 24), the prevalence of dental fluorosis (TFI score>> or = 1) was 67%, while 21% had severe fluorosis (TFI score>> or = 5). In the nonvegetarian group (n = 141) the prevalence of fluorosis and severe fluorosis was 95% and 35%, respectively. In bi-variate correlation analyses age, vegetarianism and a series of other factors related to childhood nutrition (meals per day, the use of home-made porridge, the use of fish, etc.) were significantly associated with the tooth prevalence of dental fluorosis (TPF, P < 0.05). Stepwise multiple linear regression analyses explained 30% of the variance in TPF; age 15% points and vegetarianism 13% points. Multiple logistic regression analysis showed that the risk of developing dental fluorosis was seven times higher among nonvegetarians than among vegetarians.

CONCLUSIONS

The significantly lower prevalence and severity of dental fluorosis among the vegetarian group compared to the nonvegetarians would seem to be related to diet.

BACKGROUND

Hypertension affects about 80% of people older than 80 years; however, diagnosis and treatment are difficult because about 55% of them do not adhere to treatment recommendations due to low socioeconomic status, comorbidities, age, physical limitations, and frailty syndrome.

OBJECTIVE

The purposes of this study were to evaluate the influence of frailty on medication adherence among elderly hypertensive patients and to assess whether other factors influence adherence in this group of patients.

RESULTS

The study included 296 patients (mean age 68.8±8.0) divided into frail (n=198) and non-frail (n=98) groups. The Polish versions of the Tilburg Frailty Indicator (TFI) for frailty assessment and 8-item Morisky Medication Adherence Scale for adherence assessment were used. The frail patients had lower medication adherence in comparison to the non-frail subjects (6.60±1.89 vs 7.11±1.42; P=0.028). Spearman's rank correlation coefficients showed that significant determinants with negative influence on the level of adherence were physical (rho =-0.117), psychological (rho =-0.183), and social domain (rho =-0.163) of TFI as well as the total score of the questionnaire (rho =-0.183). However, multiple regression analysis revealed that only knowledge about complications of untreated hypertension (β=0.395) and satisfaction with the home environment (β=0.897) were found to be independent stimulants of adherence level.

CONCLUSIONS

Frailty is highly prevalent among elderly hypertensive patients. Higher level of frailty among elderly patients can be considered as a determinant of lower adherence. However, social support and knowledge about complications of untreated hypertension are the most important independent determinants of adherence to pharmacological treatment.

To investigate systematic errors in traditional quantitative susceptibility mapping (QSM) where background field removal and local field inversion (LFI) are performed sequentially, to develop a total field inversion (TFI) QSM method to reduce these errors, and to improve QSM quality in the presence of large susceptibility differences.

The proposed TFI is a single optimization problem which simultaneously estimates the background and local fields, preventing error propagation from background field removal to QSM. To increase the computational speed, a new preconditioner is introduced and analyzed. TFI is compared with the traditional combination of background field removal and LFI in a numerical simulation and in phantom, 5 healthy subjects, and 18 patients with intracerebral hemorrhage.

Compared with the traditional method projection onto dipole fields+LFI, preconditioned TFI substantially reduced error in QSM along the air-tissue boundaries in simulation, generated high-quality in vivo QSM within similar processing time, and suppressed streaking artifacts in intracerebral hemorrhage QSM. Moreover, preconditioned TFI was capable of generating QSM for the entire head including the brain, air-filled sinus, skull, and fat.

Preconditioned total field inversion improves the accuracy of QSM over the traditional method where background and local fields are separately estimated. Magn Reson Med 78:303-315, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Recent studies have suggested a neuroprotective effect for vitamin B12. The present study investigated the effects of vitamin B12, diclofenac and celecoxib in separate and combined treatments on functional recovery of crushed tibial nerve in rats. In ketamine plus xylazin anesthetized rats, right tibial nerve was crushed using a small hemoatatic forceps. Footprints were recorded 1 day before and on days 7, 14 and 21 after induction of nerve injury. Tibial functional index (TFI) was used to evaluate the recovery of tibial nerve function. Histological changes of tibial nerve were investigated by light microscopy. The recovery of TFI values were significantly accelerated with 10 consecutive days treatments with 0.1 and 0.5 mg/kg of vitamin B12, 5 mg/kg of diclofenac and 1 and 5 mg/kg of celecoxib. The severity of Wallerian degeneration was reduced by above-mentioned doses of vitamin B12, diclofenac and celecoxib. Documented effects were observed when 0.1 mg/kg of vitamin B12 was concurrently used with 1 mg/kg of diclofenac and or 0.2 mg/kg of celecoxib. In the present study, vitamin B12, celecoxib and diclofenac (at a high dose) showed neuroprotective effects. Inhibition of cyclooxygenase (COX) 1 and 2 pathways may be involved in neuroprotective effect of vitamin B12.

The goal of this study was to compare treatment outcomes for chronic bothersome tinnitus after Tinnitus Retraining Therapy (TRT) versus standard of care treatment (SC) and to determine the longevity of the effect over an 18-month period.

A randomized controlled trial comparing TRT to SC for chronic tinnitus.

Adults with subjective, stable, bothersome chronic tinnitus associated with hearing loss amenable to aural rehabilitation with hearing aids were recruited. The Tinnitus Handicap Inventory (THI) was the primary outcome measure and the Tinnitus Functional Index (TFI) the secondary outcome measure of tinnitus severity and impact. Data were collected at screening, entry (0 months), and 6, 12, and 18 months after the beginning of treatment, using an integrated digitized suite of evaluation modules. TRT consisted of directive counseling and acoustic enrichment using combination hearing aids and sound generators; SC consisted of general aural rehabilitation counseling and hearing aids.

Significant improvement in tinnitus impact occurred after both TRT and SC therapy, with a larger treatment effect obtained in the TRT group. Lasting therapeutic benefit was evident at 18 months in both groups. THI initial scores were unstable in 10% of enrolled participants, showing moderate bidirectional fluctuation between screening and baseline (0 month) assessment.

Adults with moderate to severe tinnitus and hearing loss amenable to amplification, benefit from either TRT or SC treatment when combined with hearing aid use. TRT benefit may exceed that of SC. The global improvement in tinnitus severity that accrued over an 18-month period appeared to be robust and clinically significant.

I.

BACKGROUND

Whereas hearing aids have long been considered effective for providing relief from tinnitus, controlled clinical studies evaluating this premise have been very limited.

OBJECTIVE

The purpose of this study was to systematically determine the relative efficacy of conventional receiver-in-the-canal hearing aids (HA), the same hearing aids with a sound generator (HA+SG), and extended-wear, deep fit hearing aids (EWHA), to provide relief from tinnitus through a randomized controlled trial. Each of these ear-level devices was a product of Phonak, LLC.

METHODS

Participants were randomized to HA, HA+SG, or EWHA and wore bilaterally fit devices for about 4 months. Fittings, adjustments, and follow-up appointments were conducted to comply with company guidelines and to ensure that all participants attended appointments on the same schedule. At 4-5 months, participants returned to complete final outcome measures, which concluded their study participation.

METHODS

Participants were 55 individuals (mean age: 63.1 years) with mild to moderately-severe hearing loss who: (a) did not currently use hearing aids; (b) reported tinnitus that was sufficiently bothersome to warrant intervention; and (c) were suitable candidates for each of the study devices.

METHODS

The primary outcome measure was the Tinnitus Functional Index (TFI). Secondary outcome measures included hearing-specific questionnaires and the Quick Speech in Noise test (QuickSIN). The goal of the analysis was to evaluate efficacy of the EWHA and HA+SG devices versus the HA standard device.

RESULTS

There were 18 participants in each of the HA and EWHA groups and 19 in the HA+SG group. Gender, age, and baseline TFI severity were balanced across treatment groups. Nearly all participants had a reduction in tinnitus symptoms during the study. The average TFI change (improvement) from baseline was 21 points in the HA group, 31 points in the EWHA group, and 33 points in the HA+SG group. A "clinically significant" improvement in reaction to tinnitus (at least 13-point reduction in TFI score) was seen by 67% of HA, 82% of EWHA, and 79% of HA+SG participants. There were no statistically significant differences in the extent to which the devices reduced TFI scores. Likewise, the hearing-specific questionnaires and QuickSIN showed improvements following use of the hearing aids but these improvements did not differ across device groups.

CONCLUSIONS

There is insufficient evidence to conclude that any of these devices offers greater relief from tinnitus than any other one tested. However, all devices appear to offer some improvement in the functional effects of tinnitus.

Chlamydia trachomatis is the most frequently detected agent of sexually transmitted infections worldwide. Infection of the lower female genital tract (FGT) can cause cervicitis and if ascending to the upper FGT may result in serious sequelae such as pelvic inflammatory disease (PID), salpingitis and tubal factor infertility (TFI). The factors leading to this complication are still not completely understood. We elaborate four different models for host-pathogen interactions in C. trachomatis infections that may promote disease development: (1) acute infection, (2) repeated infections, (3) chronic/persistent infections and (4) non-inflammatory colonization. Whereas experimental data exist for all of these models in vitro, ex vivo and in vivo, we were interested in seeing what clinical evidence we have supporting one or the other model. We particularly focused on data that favour the one or the other model for TFI development in C. trachomatis infection and speculate on future studies that could integrate in vitro findings for a better characterization of the situation in vivo.

BACKGROUND

Frailty syndrome (FS) is an important problem in older persons. It may develop concomitantly to many aging-related diseases, including arterial hypertension, and exerts detrimental effects on both their outcomes and treatment compliance.

OBJECTIVE

To analyze the effect of FS on treatment compliance in older hypertensive patients.

METHODS

This study of 300 hypertensive patients (167 women and 133 men) aged between 65 and 91 years (mean 71.75±7.79 years) was based on the analysis of medical documentation and survey with the Tilburg Frailty Indicator (TFI) and Hill-Bone High Blood Pressure Compliance Scale.

RESULTS

Mean systolic and diastolic blood pressure values of the study subjects were 141.97 and 85.16 mm Hg, respectively. Mean time elapsed since the diagnosis of arterial hypertension was 13.74 years. FS was diagnosed in 65.67% of the study subjects. Mean global score of the Hill-Bone High Blood Pressure Compliance Scale was 20.75 points. TFI scores correlated significantly with the global score of the Hill-Bone High Blood Pressure Compliance Scale (R=0.509, P<0.001) and the values of its 2 subscales: Appointment Keeping (R=0.34, P<0.001) and Medication Taking (R=0.537, P<0.001).

CONCLUSIONS

FS exerts a significant effect on treatment compliance of older hypertensive patients. Treatment compliance is modulated by patients' sex (worse compliance in men), education (better compliance in subjects with higher education), and TFI scores (worse compliance in patients with FS).

The aim of this study was to analyze the molecular structure of enamel with fluorosis using micro-Raman spectroscopy and compare it with that of healthy enamel. Eighty extracted human molars were classified into four fluorosis groups according to the Thylstrup-Fejerskov Index (TFI) [TFI: 0, Healthy enamel; 1-3, mild; 4-5, moderate; 6-9, severe fluorosis]. All samples were analyzed by micro-Raman spectroscopy. The integral areas of ν(1) (960 cm(-1)) phosphate peak as well as B-type carbonate peak (1070 cm(-1)) were obtained to analyze structural differences among the specimens. Although the differences were not statistically significant (P>> 0.05), the mean of integral areas of ν(1) phosphate peak among groups indicated greater mineralization in the severe fluorosis group. However, there were statistically significant differences in the intensities, and the integral areas of B-type carbonate peak among groups (P < 0.05). Therefore, mineralization of the carbonate peak at 1070 cm(-1) decreased significantly in fluorotic groups, suggesting that carbonate ions are easily dissolved in the presence of fluoride. Although structurally fluorotic teeth are not more susceptible to dental caries, serious alteration in its surface topography may cause retention of bacterial plaque and formation of enamel caries. Micro-Raman spectroscopy is a useful tool for analyzing the molecular structure of healthy and fluorotic human enamel.

OBJECTIVE

The aim of this study was to identify sociodemographic and behavioural factors associated with the prevalence of severe dental fluorosis in moderate- and high-fluoride areas of the Ethiopian Rift Valley.

METHODS

Three hundred and six adolescents (12-15 years) and 233 mothers participated in the study. The children were examined for dental fluorosis according to the Thylstrup-Fejerskov Index (TFI). The children and their mothers were subsequently interviewed. Sixty mothers had more than one participating child. In order to perform a paired parent/child analysis, a total of 73 younger siblings had to be excluded.

RESULTS

Among the remaining 233 children, the prevalence of severe dental fluorosis (TFI>>or= 5) was 24.1% and 75.9% in the moderate- and high-fluoride areas, respectively. According to bivariate as well as multivariate analyses, a number of sociodemographic and behavioural factors were related to severe fluorosis. The odds for having severe fluorosis varied according to the fluoride concentration of the drinking water, age, consumption of tea, length of breastfeeding and method of storing water. The adjusted odds ratios ranged from 2.6 to 26.1. Breastfeeding for>> 18 months and the use of clay pots for storing drinking water helped protect against severe dental fluorosis. Bivariate analyses indicated that being male and consuming fish might be associated with higher TFI scores.

CONCLUSIONS

In order to avoid dental fluorosis, low-fluoride drinking water should be provided in the relevant villages. A prolonged period of breastfeeding, the use of clay pots for storing water, and possibly a reduced intake of tea and whole fish in infants might also help to avoid severe fluorosis in children growing up in traditionally fluoride-endemic areas.

OBJECTIVE

Injury to the anterior cruciate ligament (ACL) is frequently accompanied by tears of the menisci. Some of these tears occur at the time of injury, but others develop over time in the ACL-deficient knee. The aim of this study was to evaluate the effects of the patient characteristics, time from injury (TFI), and posterior tibial slope (PTS) on meniscal tear patterns. Our hypothesis was that meniscal tears would occur more frequently in ACL-deficient knees with increasing age, weight, TFI, PTS, and in male patients.

METHODS

Of the ACL-injured patients, 362 were analyzed, and details of meniscal lesions were collected. The medial and lateral tibial slopes (MTS, LTS) were measured via computed tomography. Patient demographics, TFI, MTS, and LTS were correlated with the diagnosed meniscal tears.

RESULTS

Of the patients, 113 had a medial meniscus (MM) tear, 54 patients had a lateral meniscus (LM) tear, 34 patients had tears of both menisci, and 161 patients had no meniscal tear. The most common tear location was the posterior horn (PH) of the MM, followed by tear involving the whole MM. Patient age, BMI, and TFI were significantly associated with the incidence of MM tear. Female patients had a higher incidence of injury than males in all tear sites except in the body and PH. Male patients had more vertical and peripheral tears. The median MTS and LTS for patients with MM tears were 7.0°and 8.7°, respectively, while those of patients with LM tears were 6.9° and 8.1°. Steeper LTS was significantly associated with tears of LM and of both menisci.

CONCLUSIONS

Older age, male sex, increased BMI, and prolonged TFI were significant factors for the development of MM tears. An increase in the tibial slope, especially of the lateral plateau, seems to increase the risk of tear of the LM and of both menisci.

METHODS

Level III.

Hepatocyte nuclear factor 1 (HNF1) is a liver-enriched transcription factor that plays an important role in transcriptional networks involved in liver function. The promoters of mammalian HNF1 genes contains a single binding site for another liver-enriched transcription factor, the nuclear hormone receptor HNF4. A transcriptional hierarchy involving HNF4-mediated activation of the HNF1 promoter has been proposed to be of crucial importance in maintaining the differentiated hepatocyte phenotype. Here we present evidence that the Atlantic salmon HNF1 promoter contains three nuclear-hormone-receptor-binding sequences. Gel-shift assays showed that these motifs are recognized with different affinities by HNF4 and the orphan nuclear receptors chicken ovalbumin upstream promoter transcription factors COUP-TFI and COUP-TFII. In hepatoma cells, the site showing highest affinity for HNF4 appears to be crucial for promoter activity. Transfection experiments in non-hepatic cells indicated that the salmon HNF1 promoter was activated by both HNF4 and COUP-TFs. We also identified a promoter fragment encompassing the two more distal nuclear-hormone-binding sites that was activated by HNF4, unaffected by COUP-TF and showed a strong synergistic activation by HNF4/COUP-TF. Results are presented detailing these interactions in relation to the salmon HNF1 promoter architecture.

The cellular diversity of neurons located in the marginal zone (MZ) of the cortex has a crucial role in cortical development. However, little is known about the molecular mechanisms involved in how these different neuronal cell types are specified. Here, we show that in the MZ, the nuclear receptor COUP-TFI is localized in calbindin-positive cells and not in reelin-positive cells. High expression of COUP-TFI has been detected in preplate (PP) and subplate (SP) cells, suggesting that this nuclear receptor is down-regulated during preplate differentiation towards the Cajal-Retzius (CR) cell lineage. By maintaining high ectopic expression of COUP-TFI in preplate cells, we show that COUP-TFI represses the CR cell markers reelin and calretinin, and with lower efficiency the transcription factor Tbr1. Furthermore, general differentiation is not affected, strongly suggesting that COUP-TFI represses differentiation of CR cells.

BACKGROUND

The backup force of a guiding catheter is important for successful percutaneous coronary intervention (PCI), however, no theory has been proposed thus far regarding the factors involved in its generation.

RESULTS

The backup force of guiding catheters was measured in an arterial tree model. In vitro modeling showed that larger-sized guiding catheters had greater backup force (8 Fr>> 7 Fr>> 6 Fr). Comparing the backup force between transfemoral (TFI) and transradial interventions (TRI), it was found to be 60% greater in TFI with a Judkins L (JL) catheter, and 8% greater in TFI with a backup (EBU/XB) type catheter. However, the Ikari L (IL) catheter generated a similar backup force between TRI and TFI. In TRI, the Ikari guiding catheter showed the greatest backup force, especially in the power position (power position of IL4>> IL4>> backup type 3.5>> deep engagement of JL4>> JL3.5>> JL4). These findings were associated with the angle of the catheter on the reverse side of the aorta. We then constructed several catheters with varying contact lengths. In vitro modeling showed that a longer contact area increased the backup force.

CONCLUSIONS

The present model showed that three factors were associated with backup force: (1) catheter size; (2) angle on the reverse side of the aorta; and (3) contact area. The Ikari guiding catheter comprises all of the preferable factors in TRI.

Staging systems and laboratory features help predict survival in chronic lymphocytic leukaemia but they do not distinguish patients who will progress from those whose disease will remain indolent. CD38 expression has emerged as an independent prognostic factor, yet there is debate as to what level of CD38 affects prognosis. We plotted the hazard ratios for the treatment-free interval (TFI) between the higher and lower groups defined by CD38 cut-offs from 0 to 100%. The maximum hazard ratio was achieved for a cut-off of 7%. We examined by triple colour analysis the values for CD38 in 289 untreated patients using both>>or=30 and>>or=7% as thresholds for prognosis. Using a>>or=7% threshold (but not>>or=30%), we showed a significant correlation with advanced stage and male sex. The interval from diagnosis to first therapy or TFI was longer (median 36 months) in patients with <7% CD38 positive cells than those with>>or= 30% (8.7 months) or with intermediate values between 7 and 29% (P<0.00005). The <7% threshold also identified patients in stage A with a long TFI (P=0.0001). Multivariate analysis showed that CD38 has independent prognostic value for TFI in all patients. In 135 patients tested for deletions of p53, 13q14 and 11q23 and for trisomy 12, we showed a correlation between 13q14 deletion and <30%/<7% CD38 positive cells and a tendency for trisomy 12 to be associated with>>or=30%>>or=7% CD38 positive cells. We conclude that 7% may be a more useful threshold for disease progression than higher values of CD38.

The relationships between impaired cortical development and consequent malformations in neurodevelopmental disorders, as well as the genes implicated in these processes, are not fully elucidated to date. In this study, we report six novel cases of patients affected by BBSOAS (Boonstra-Bosch-Schaff optic atrophy syndrome), a newly emerging rare neurodevelopmental disorder, caused by loss-of-function mutations of the transcriptional regulator NR2F1. Young patients with NR2F1 haploinsufficiency display mild to moderate intellectual disability and show reproducible polymicrogyria-like brain malformations in the parietal and occipital cortex. Using a recently established BBSOAS mouse model, we found that Nr2f1 regionally controls long-term self-renewal of neural progenitor cells via modulation of cell cycle genes and key cortical development master genes, such as Pax6. In the human fetal cortex, distinct NR2F1 expression levels encompass gyri and sulci and correlate with local degrees of neurogenic activity. In addition, reduced NR2F1 levels in cerebral organoids affect neurogenesis and PAX6 expression. We propose NR2F1 as an area-specific regulator of mouse and human brain morphology and a novel causative gene of abnormal gyrification.

Keywords: NR2F1/COUP-TFI; BBSOAS; cell cycle dynamics; cortical folding; neurodevelopmental disease.

OBJECTIVE

At present, it remains unclear whether the third-line chemotherapy has clinical benefit. In this study, we retrospectively evaluated the effect of third-line chemotherapy.

METHODS

We reviewed the medical records of 40 women with recurrent epithelial ovarian cancer (EOC) who received third-line chemotherapy after platinum/taxan regimens as first line chemotherapy.

RESULTS

In the first recurrence, 23 cases were platinum-sensitive and 17 cases were platinum-resistant. The cases for which the treatment-free interval from second-line chemotherapy (TFI) was a 3 months had a higher non-PD rate than those with TFI < 3 months (86% vs 33%, p = 0.002). In addition, the median overall survival (OS) was longer for TFI>> or = 3 months than for TFI < 3 months (1195 days vs 235 days, p = 0.004). Finally, TFI was an independent significant prognostic factor by univariate (HR 3.28, p = 0.006) and multivariate (HR 3.21, p = 0.018) proportional hazard tests.

CONCLUSIONS

TFI from second-line chemotherapy may predict a survival benefit of third-line chemotherapy.

The goal of this study was to determine the factors associated with response to platinum retreatment in patients with platinum-resistant ovarian cancer. A review of patients with epithelial ovarian cancer retreated with cisplatin or carboplatin between 2002 and 2004 was performed. The platinum-free interval (PFI) and treatment-free interval (TFI) were determined for each patient. Response was based on serial CA125 levels using a modification of the Rustin criteria. Patients with clinical benefit ([CB] those who attained at least stable disease) were compared to patients with disease progression (PD). An analysis was performed to determine factors associated with CB in platinum-resistant patients retreated with platinum. Of 48 patients identified, 37 were evaluable included in this analysis. CB was observed in 27 (73%) while disease progression was noted in 10 (27%) women. The PFI was longer in those women who achieved CB (12.3 vs 6.9 months; P = 0.02). The TFI was 7.1 months for patients benefited from platinum retreatment vs 3.5 months for those with disease progression (P = 0.06). There was no statistically significant difference in the number of cytotoxic agents between the time of platinum retreatment and the prior platinum regimen (2 vs 1.5 months; P = 0.61). A prolonged PFI was associated with an improved chance of achieving CB with platinum retreatment. There was no association between the response to platinum retreatment and the number of intervening cytotoxic agents utilized. Further prospective study is warranted to define the optimal timing of platinum retreatment.

OBJECTIVE

This study aimed to determine the predictive value of the Brazilian Tilburg Frailty Indicator (TFI) for adverse health outcomes (falls, hospitalization, disability and death), in a follow-up period of twelve months.

METHODS

This longitudinal study was carried out with a sample of people using primary health care services in Rio de Janeiro, Brazil. At baseline the sample consisted of 963 people aged 60 years and older. A subset of all respondents participated again one year later (n = 640, 66.6% response rate). We used the TFI, the Katz's scale for assessing ADL disability and the Lawton Scale for assessing IADL disability. Falls, hospitalization and death were also assessed using a questionnaire.

RESULTS

The prevalence of frailty was 44.2% and the mean score of the TFI was 4.4 (SD = 3.0). There was a higher risk of loss in functional capacity in ADL (OR = 3.03, CI95% 1.45-6.29) and in IADL (OR = 1.51, CI95% 1.05-2.17), falls (OR = 2.08, CI95% 1.21-3.58), hospitalization (OR = 1.83, CI95% 1.10-3.06), and death (HR = 2.73, CI95% 1.04-7.19) for frail when compared to non-frail elderly, in the bivariate analyses. Controlling for the sociodemographic variables, the frailty domains together improved the prediction of hospitalization, falls and loss in functional capacity in ADL, but not loss in functional capacity in IADL.

CONCLUSIONS

The TFI is a good predictor of adverse health outcomes among elderly users of primary care services in Brazil and appears an adequate and easy to administer tool for monitoring their health conditions.

Chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) is an orphan member of the nuclear hormone receptor superfamily that comprises key regulators of many biological functions, such as embryonic development, metabolism, homeostasis, and reproduction. Although COUP-TFI can both actively silence gene transcription and antagonize the functions of various other nuclear receptors, the COUP-TFI orphan receptor also acts as a transcriptional activator in certain contexts. Moreover, COUP-TFI has recently been shown to serve as an accessory factor for some ligand-bound nuclear receptors, suggesting that it may modulate, both negatively and positively, a wide range of hormonal responses. In the absence of any identified cognate ligand, the mechanisms involved in the regulation of COUP-TFI activity remain unclear. The elucidation of several putative phosphorylation sites for MAPKs, PKC, and casein kinase II within the sequence of this orphan receptor led us to investigate phosphorylation events regulating the various COUP-TFI functions. After showing that COUP-TFI is phosphorylated in vivo, we provide evidence that in vivo inhibition of either MAPK or PKC signaling pathway leads to a specific and pronounced decrease in COUP-TFI-dependent transcriptional activation of the vitronectin gene promoter. Focusing on the molecular mechanisms underlying the MAPK- and PKC-mediated regulation of COUP-TFI activity, we show that COUP-TFI can be directly targeted by PKC and MAPK. These phosphorylation events differentially modulate COUP-TFI functions: PKC-mediated phosphorylation enhances COUP-TFI affinity for DNA and MAPK-mediated phosphorylation positively regulates the transactivation function of COUP-TFI, possibly through enhancing specific coactivator recruitment. These data provide evidence that COUP-TFI is likely to integrate distinct signaling pathways and raise the possibility that multiple extracellular signals influence biological processes controlled by COUP-TFI.

Tumor of the follicular infundibulum (TFI) is an uncommon benign adnexal tumor that usually presents as a solitary keratotic papule on the face or scalp of elderly patients. Histopathologically, it typically manifests as a plate-like fenestrated proliferation of monomorphic pale-staining cells. A 76-year-old male presented with about a 2 cm, well-defined, yellowish to brownish, slightly elevated, twisted and bent, interrupted, cord-like plaque on his left lower abdomen. Microscopic examination revealed a sharply demarcated plate-like proliferation of pale cells localized in the papillary dermis with multiple connections to the overlying epidermis. The histopathological features were compatible with TFI, except for foci of sebaceous differentiation. There has been one previous case report of TFI with sebaceous differentiation in the English medical literature. Herein, we report on a singular case of TFI with sebaceous differentiation.

BACKGROUND

Transcriptional regulation of gene expression in eukaryotes is usually accomplished by cooperative transcription factors (TFs). Computational identification of cooperative TF pairs has become a hot research topic and many algorithms have been proposed in the literature. A typical algorithm for predicting cooperative TF pairs has two steps. (Step 1) Define the targets of each TF under study. (Step 2) Design a measure for calculating the cooperativity of a TF pair based on the targets of these two TFs. While different algorithms have distinct sophisticated cooperativity measures, the targets of a TF are usually defined using ChIP-chip data. However, there is an inherent weakness in using ChIP-chip data to define the targets of a TF. ChIP-chip analysis can only identify the binding targets of a TF but it cannot distinguish the true regulatory from the binding but non-regulatory targets of a TF.

RESULTS

This work is the first study which aims to investigate whether the performance of computational identification of cooperative TF pairs could be improved by using a more biologically relevant way to define the targets of a TF. For this purpose, we propose four simple algorithms, all of which consist of two steps. (Step 1) Define the targets of a TF using (i) ChIP-chip data in the first algorithm, (ii) TF binding data in the second algorithm, (iii) TF perturbation data in the third algorithm, and (iv) the intersection of TF binding and TF perturbation data in the fourth algorithm. Compared with the first three algorithms, the fourth algorithm uses a more biologically relevant way to define the targets of a TF. (Step 2) Measure the cooperativity of a TF pair by the statistical significance of the overlap of the targets of these two TFs using the hypergeometric test. By adopting four existing performance indices, we show that the fourth proposed algorithm (PA4) significantly out performs the other three proposed algorithms. This suggests that the computational identification of cooperative TF pairs is indeed improved when using a more biologically relevant way to define the targets of a TF. Strikingly, the prediction results of our simple PA4 are more biologically meaningful than those of the 12 existing sophisticated algorithms in the literature, all of which used ChIP-chip data to define the targets of a TF. This suggests that properly defining the targets of a TF may be more important than designing sophisticated cooperativity measures. In addition, our PA4 has the power to predict several experimentally validated cooperative TF pairs, which have not been successfully predicted by any existing algorithms in the literature.

CONCLUSIONS

This study shows that the performance of computational identification of cooperative TF pairs could be improved by using a more biologically relevant way to define the targets of a TF. The main contribution of this study is not to propose another new algorithm but to provide a new thinking for the research of computational identification of cooperative TF pairs. Researchers should put more effort on properly defining the targets of a TF (i.e. Step 1) rather than totally focus on designing sophisticated cooperativity measures (i.e. Step 2). The lists of TF target genes, the Matlab codes and the prediction results of the four proposed algorithms could be downloaded from our companion website http://cosbi3.ee.ncku.edu.tw/TFI/.