BACKGROUND

Sleep loss may induce endothelial dysfunction, a key factor in cardiovascular risk. We examined the endothelial function during one week of sleep restriction and a recovery period (from 3-to-13 days) in healthy subjects, and its link to autonomic, inflammatory and/or endocrine responses.

METHODS

12 men were followed at baseline (B1, 8-h sleep), after 2 (SR2) and 6 (SR6) days of SR (4-h sleep: 02:00-06:00) and after 1 (R1) and 12 (R12) recovery nights (8h sleep). At 10:00, we assessed changes in: arm cutaneous vascular conductance (CVC) induced by local application of methacholine (MCh), cathodal current (CIV) and heat (44°C), finger CVC and skin temperature (Tfi) during local cold exposure (5°C, 20-min) and passive recovery (22°C, 20-min). Blood samples were collected at 08:00.

RESULTS

Compared with baseline (B1), MCh and heat-induced maximal CVC values (CVC peak) were decreased at SR6 and R1. No effect of SR was observed for Tfi and CVC during immersion whereas these values were lower during passive recovery on SR6 and R1. From SR2 to R12, plasma concentrations of insulin, IGF-1 (total and free) and MCP-1 were significantly increased while those of testosterone and prolactin were decreased. Whole-blood blood mRNA concentrations of TNF-α and IL-1β were higher than B1. No changes in noradrenaline concentrations, heart rate and blood pressure were observed.

CONCLUSIONS

These results demonstrate that SR reduces endothelial-dependent vasodilatation and local tolerance to cold. This endothelial dysfunction is independent of blood pressure and sympathetic activity but associated with inflammatory and metabolic pathway responses (ClinicalTrials-NCT01989741).

The nucleotide sequence (8396 nucleotides) was determined, from the 3'-end of the putative polymerase gene to the poly(A) tail, for a Taiwanese virulent isolate, TFI, of transmissible gastroenteritis virus (TGEV). The TFI nucleotide sequence had very high identity to the British virulent field isolate FS772/70 (98.3%), the attenuated Purdue 115 (96.7%) and from the S gene to ORF-4 gene region, to the low passaged virulent Miller (98.3%) strains of TGEV. Comparison of the TFI S protein sequence with those determined from other TGEV strains and those of the TGEV variant, porcine respiratory coronavirus, isolated from Europe and North America showed that they had changed very little over a period of 4 decades. The two extra amino acids found to be present in the spike proteins of the virulent FS772/70 and Miller strains when compared to the avirulent Purdue strain were found to be present in the TFI strain. The genomic organisation of the TFI strain was the same as that of the other TGEV viruses.

Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) and steroidogenic factor-1 (SF-1) play key roles in the transcriptional regulation of steroidogenic P450 genes. Transfection studies showed that SF-1 activated bovine CYP17 promoter activity, whereas COUP-TFs repressed it from the CRS2 element in a mutually exclusive manner in mouse adrenocortical Y-1 cells. COUP-TFI and SF-1 competitively bind to the Ad5 element of the human CYP11B2 gene promoter. Unexpectedly, overexpression of COUP-TFI increased the CYP11B2 promoter activity, whereas overexpression of SF-1 repressed it in human adrenocortical H295R cells. In cortisol-producing adrenal cortical adenomas, down-regulation of nuclear receptors, including COUP-TFs was found. We therefore screened for COUP-TFI-interacting proteins using a yeast two-hybrid system and have identified Ubc9 and PIAS1, SUMO-1 conjugating enzyme and ligase, respectively. Coexpression of Ubc9 and PIAS1 synergistically enhanced COUP-TFI-mediated trans-repression of CYP17 gene as well as transactivation of CYP11B2 gene. The SUMOylation-defective mutants of these proteins continued to function as co-regulators of COUP-TFI. These findings indicate that Ubc9 and PIAS1 can function as transcriptional co-regulators of COUP-TFI to modulate adrenal cortical steroidogenesis in a SUMOylation-independent manner.

OBJECTIVE

Using a statistical modelling approach, our study aim is to determine reliable age-related estimates of the risk of all-cause tubal factor infertility (TFI) following past or current chlamydial infection in women in Scotland.

METHODS

Using data from several sources, a Markov-Chain Monte Carlo model was used to estimate the age-related risk of TFI given genital chlamydia infection at any time. The analysis is based on the probability of a woman ever having chlamydial infection, ever having TFI and ever having a previous chlamydial infection given a diagnosis of TFI. The model was programmed and evaluated using WinBugs14.

RESULTS

By the age 44 years, the overall risk of a woman having at least a single chlamydial infection is estimated at 42.9% (95% credible interval 30.0, 59.0%). The risk of a woman having TFI increased from 0.5% in those aged 16-19 years to 0.8% in those aged 40-44. The overall estimated probability of TFI, based on lifetime infertility, given a past or current chlamydial infection, is relatively consistent across all five age groups from 16-44 years, being 0.9% among those aged 25-29 and 1.4% in those aged 35-39; The estimates were found to be sensitive to the definition of infertility, with the estimate increasing from 1.3% in the youngest age group to 2.8% and 4.5% for 24-month primary infertility and primary or secondary infertility, respectively.

CONCLUSIONS

At the population level, the likelihood of all-cause TFI in those with past or current chlamydial infection is low. These findings have relevance both at the policy level, in the development of control programmes, and also at an individual level, particularly for clinicians supporting women undergoing testing or with a positive diagnosis.

OBJECTIVE

Testosterone (T) is assumed to be a risk factor for coronary artery disease (CAD). However, recent studies have demonstrated a beneficial effect of T on myocardial ischaemia in men with CAD. To assess the potential role of T in CAD in postmenopausal women we investigated the association between T level and CAD and relationship between T and other CAD metabolic risk factors.

RESULTS

Within the 12-month study period, 108 consecutive, postmenopausal women (age 62+/-7 years) referred for diagnostic coronary angiography were prospectively included in the study. In all patients serum level of T, sex hormone-binding globulin (SHBG), total cholesterol (T-chol), LDL-chol, HDL-chol, triglycerides (TG), apolipoproteins A(1) and B (apo A(1), apo B), lipoprotein a [Lp(a)], and C reactive protein were measured. Testosterone free index (TFI) was calculated as Tx100/SHBG. CAD was documented in 51 (47%) patients (CAD+). Women with CAD had decreased T level and lower TFI (T: 0.99+/-0.4 vs. 1.41+/-0.7 nmol/l, P=0.005; TFI: 3.2+/-1.4 vs. 4.2+/-2.2, P=0.04, CAD+ vs. CAD-, respectively). No difference in SHBG was found between the two groups. In 16 women (six CAD+, 10 CAD-) who were on hormonal replacement therapy (HRT+) we observed significantly elevated T level and TFI (T: 1.62+/-0.5 vs. 1.15+/-0.7 nmol/l; TFI: 5.0+/-2.2 vs. 3.5+/-1.8, HRT+ vs. HRT-, respectively, P<0.05). When these women were excluded from the analysis, T level remained decreased in CAD+ group (0.96+/-0.4 vs. 1.22+/-0.5 nmol/l, CAD+ vs. CAD- respectively, P<0.02). CAD+ group had an unfavourable profile of metabolic CAD risk factors as evidenced by elevated T-chol, LDL-chol, Lp(a), apoB, and decreased apoA(1) (P<0.05 vs. CAD- in all comparisons). Neither T nor TFI correlated with CAD metabolic risk factors (r<0.2, P>0.1 for all correlations), apart from an inverse correlation between T and Lp(a) (r=-0.24, P=0.04).

CONCLUSIONS

In postmenopausal women decreased T level is associated with CAD independently of the other CAD metabolic risk factors. Hormonal replacement therapy tends to increase T level which may further support the beneficial role of HRT in postmenopausal women.

OBJECTIVE

The present study was conducted to assess dental fluorosis and to compare fluorosis in incisor teeth among 13- to 15-year-old school children of Nalgonda district, Andhra Pradesh.

METHODS

Cross-sectional analytical study was conducted. A total of 1000 school children aged 13 to 15 years were selected by stratified cluster sampling from 4 different areas with different levels of naturally occurring fluoride in drinking water. Fluorosis was recorded using TF index (TFI).

RESULTS

Prevalence of fluorosis (TFI score,>> or = 1) was 100% at all the 4 different fluoride levels. The prevalence and severity increased with increased fluoride levels in drinking water. Prevalence and severity of fluorosis did not show any significant variation between maxillary and mandibular incisor teeth.

CONCLUSIONS

There is a high prevalence of mild-to-moderate fluorosis in Nalgonda district, even in areas with optimal fluoride levels in water.

The aim of this work was to determine the effects of age, severity of fluorosis, and etching time on the shear bond strength of direct composite resin to human enamel. A total of 117 teeth, freshly extracted from patients in areas of Saudi Arabia endemic for dental fluorosis, were classified according to age (< 40 years and 40+ years) and severity of fluorosis, using the Thylstrup and Fejerskov index, TFI: TFI = 0, TFI = 1-3, and TFI = 4-6. Cylindrical composite resin specimens 5 mm in diameter and 3 mm high were bonded to the flattened midlabial enamel surfaces etched for 60 or 120 seconds and shear bond strength measured, using the Instron Universal Testing Machine at a crosshead speed of 0.5 mm/minute. Shear bond strength of the resin varied between 11.2 +/- 3.6 and 21.6 +/- 4.1 MPa. Three-way analysis of variance and Sheffé's multiple range test showed that the severity of fluorosis had no statistically significant effect on shear bond strength (p>> 0.05). However, the bond was significantly stronger in teeth from patients < 40 years old than from those 40+ years old. Furthermore, at age < 40 years, shear bond strength was significantly higher in teeth etched for 120 seconds than those etched for 60 seconds (p < 0.05), but this was not the case in teeth from the older patients. In teeth with TFI = 1-3, the mode of bond failure was predominantly mixed, but at TFI = 4-6, the bond failure was mostly cohesive in enamel at all ages and etching times. It is, therefore, concluded that both age and etching time affect the shear bond strength of composite resin to fluorosed human enamel.

Direct repeat motifs composed of two hexamer half-sites spaced by a single nucleotide (DR-1) are recognized by several members of the nuclear hormone receptor superfamily. We examined, by means of gene transfection assays, the interplay between the DR-1-binding nuclear receptors commonly expressed in liver, peroxisome proliferator-activated receptor alpha (PPARalpha), hepatocyte nuclear factor-4 (HNF-4), and chicken ovalbumin upstream transcription factor I (COUP-TFI). Both PPARalpha and HNF-4 efficiently bound to the acyl-CoA oxidase gene enhancer element, but PPARalpha exhibited much stronger transactivation than HNF-4. As a result, HNF-4 suppressed the gene-activating function of PPARalpha, when they were expressed together, due to competition for a common binding site. On the other hand, HNF-4, but not PPARalpha, effectively bound to the apolipoprotein CIII gene element, and activated gene transcription. PPARalpha had no effect even when co-expressed with HNF-4. COUP-TFI bound to both elements, and suppressed the gene activation by PPARalpha and HNF-4. Thus, these nuclear receptors have individual functions in gene regulation, and exhibit complex compound effects when they co-exist.

OBJECTIVE

The Rosenberg Self-Esteem Scale (RSES) is a widely used instrument that has been tested for reliability and validity in many settings; however, some negative-worded items appear to have caused it to reveal low reliability in a number of studies. In this study, we revised one negative item that had previously (from the previous studies) produced the worst outcome in terms of the structure of the scale, then re-analyzed the new version for its reliability and construct validity, comparing it to the original version with respect to fit indices.

METHODS

In total, 851 students from Chiang Mai University (mean age: 19.51±1.7, 57% of whom were female), participated in this study. Of these, 664 students completed the Thai version of the original RSES - containing five positively worded and five negatively worded items, while 187 students used the revised version containing six positively worded and four negatively worded items. Confirmatory factor analysis was applied, using a uni-dimensional model with method effects and a correlated uniqueness approach.

RESULTS

The revised version showed the same level of reliability (good) as the original, but yielded a better model fit. The revised RSES demonstrated excellent fit statistics, with χ²=29.19 (df=19, n=187, p=0.063), GFI=0.970, TFI=0.969, NFI=0.964, CFI=0.987, SRMR=0.040 and RMSEA=0.054.

CONCLUSIONS

The revised version of the Thai RSES demonstrated an equivalent level of reliability but a better construct validity when compared to the original.

OBJECTIVE

This study aimed to assess the perceived oral health status and to explore its relationship with clinically assessed dental fluorosis among school children in Arusha town, Tanzania.

METHODS

A total of 478 students (mean age 15.7 years) completed questionnaires administered in the schools during May to July 2000. Clinical photos of the upper and lower incisors were taken under field conditions. A total of 461 slides were rated under laboratory conditions. The severity of dental fluorosis in the permanent maxillary central incisors was assessed using the Thylstrup & Fejerskov Index (TFI).

RESULTS

The prevalence of dental fluorosis at TFI score>> or = 2 was 74%. A total of 67% of boys and 70% of girls rated their teeth as yellow to brown, 58% of boys and 68% of girls (P < 0.05) confirmed dissatisfaction with their dental appearance. Kappa values of 0.40-0.44 were obtained between dental fluorosis (TFI>> or = 2) and self-reported discoloration. The proportion of school children reporting dissatisfaction with oral condition and dental appearance increased with increasing TFI scores. Stepwise multiple logistic regression analysis explained 21% and 32% of the variance in the dissatisfaction with oral condition and dental appearance scores; TFI scores 11% and 15% of variation in points, and social and psychological variables 11% and 17%.

CONCLUSIONS

Whereas dental fluorosis at different diagnostic cut-off points impacts self-rated oral health negatively, social and personal factors are as important in shaping the responses of school children to oral condition and dental appearance.

OBJECTIVE

Maintaining oral health around titanium implants is essential. The formation of a biofilm on the titanium surface will influence the continuing success of the implant. These concerns have led to modified ultrasonic scaler instruments that look to reduce implant damage while maximising the cleaning effect. This study aimed to assess the effect of instrumentation, with traditional and modified ultrasonic scalers, on titanium implant surfaces and to correlate this with the oscillations of the instruments.

METHODS

Two ultrasonic insert designs (metallic TFI-10 and a plastic-tipped implant insert) were selected. Each scaler probe was scanned using a scanning laser vibrometer, under loaded and unloaded conditions, to determine their oscillation characteristics. Loads were applied against a titanium implant (100g and 200 g) for 10 s. The resulting implant surfaces were then scanned using laser profilometry and scanning electron microscopy (SEM).

RESULTS

Insert probes oscillated with an elliptical motion with the maximum amplitude at the probe tip. Laser profilometry detected defects in the titanium surface only for the metallic scaler insert. Defect widths at 200 g high power were significantly larger than all other load/power conditions (P<0.02). Using SEM, it was observed that modifications to the implant surface had occurred following instrumentation with the plastic-tipped insert. Debris was also visible around the defects.

CONCLUSIONS

Metal scalers produce defects in titanium implant surfaces and load and power are important factors in the damage caused. Plastic-coated scaler probes cause minimal damage to implant surfaces and have a polishing action but can leave plastic deposits behind on the implant surface.

Islet neogenesis, or the differentiation of islet cells from precursor cells, is seen in vitro and in vivo both embryonically and after birth. However, little is known about the differentiation pathways during embryonic development for human pancreas. Our previously reported in vitro generation of islets from human pancreatic tissue provides a unique system to identify potential markers of neogenesis and to determine the molecular mechanisms underlying this process. To this end, we analyzed the gene expression profiles of three different stages during in vitro islet generation: the Initially Adherent, Expanded, and Differentiated stages. Samples from four human pancreases were hybridized to Affymetrix U95A GeneChips, and data analyzed using GeneSpring 7.0/9.0 software. Using scatter plots we selected genes with a 2-fold or greater differential expression. Of the 12,000 genes/ESTs present on these arrays, 295 genes including 38 acinar-enriched genes were selectively lost during the progression from the Initially Adherent stage to the Expanded stage; 468 genes were increased in this progression to Expanded tissue; and 529 genes had a two-fold greater expression in the Differentiated stage than in the Expanded tissue. Besides the expected increases in insulin, glucagon, and duct markers (mucin 6, aquaporin 1 and 5), the beta cell auto-antigen IA-2/phogrin was increased 5-fold in Differentiated. In addition, developmentally important pathways, including notch/jagged, Wnt/frizzled, TGFbeta superfamily (follistatin, BMPs, and SMADs), and retinoic acid (COUP-TFI, CRABP1, 2, and RAIG1) were differentially regulated during the expansion/differentiation. Two putative markers for islet precursor cells, UCHL1/PGP9.5 and DMBT1, were enhanced during the progression to differentiated cells, but only the latter could be a marker of islet precursor cells. We suggest that appropriate manipulation of these differentiation-associated pathways will enhance the efficiency of differentiation of insulin-producing beta-cells in this in vitro model.

We examined 102 children born and reared in an area of rural Kenya with 2 ppm fluoride in the drinking water for dental fluorosis, using the index developed by Thylstrup and Fejerskov (1978). The prevalence of dental fluorosis was 100%, 92% of all teeth exhibited a TFI score of 4 or higher, and 50% of the children had pitting or more severe enamel damage in at least half the teeth present. The fluorotic changes showed a high degree of bilateral symmetry. The intra-oral distribution of the changes corresponded to the pattern of fluoride-induced enamel changes reported by other investigators in high-fluoride areas. The high prevalence and severity of dental fluorosis in a 2-ppm-fluoride area is in accordance with recent observations on dental fluorosis being very prevalent in Kenya, even in low-fluoride areas (less than 1 ppm F). We are presently investigating the possible variables which may explain this unexpected susceptibility of large populations in Eastern Africa to fluorosis from exposure to low levels of fluoride.

OBJECTIVE

To explore the impact of developmental defects of enamel (DDE) on young people, through their experiences of the condition and it's meaning to their everyday lives.

METHODS

The theoretical framework chosen to guide the study was symbolic interactionism. Qualitative interviews with a purposive sample of people aged 10-15 years with varying severities of DDE were conducted in the young person's home. The interviews were audio-taped and transcribed verbatim. The data were analysed using constant comparative method. Photographs of participants' teeth were taken and scored using the Thystrup and Fejerskov index (TFI) and the modified developmental defects of enamel index.

RESULTS

Twenty-one participants were interviewed before data saturation occurred. The TFI scores ranged from 0 to 5, 11 participants had diffuse opacities and 5 had demarcated opacities. The impact of DDE was described in terms of the degree to which young people were 'bothered' ranging from 'not bothered' to 'really quite bothered'. DDE impacted on individuals whose sense of self was defined by appearance and who depended on perceived approval from others about their appearance. No links between gender, age, severity of DDE and impact were apparent.

CONCLUSIONS

Variations in the impact of DDE were related to defining aspects of sense of self rather than the enamel defects. This research is the first to discover that the sense of self explains variation in the impact of DDE.

Telomeres are protective structures at the ends of chromosomes that have important implications for aging. To address the question of whether telomeres contribute to feline chronic kidney disease (CKD), we evaluated kidney, liver, and skin samples from 12 cats with naturally occurring CKD, 12 young normal cats, and 6 old normal cats. Telomere length was assessed using standard telomere fluorescent in situ hybridization (TEL-FISH) combined with immunohistochemistry (TELI-FISH) to identify proximal (PTEC) and distal tubular epithelial cells (DTEC), whereas senescence-associated β-galactosidase (SABG) staining was used to evaluate senescence. Results revealed statistically significant decreases in the average telomere fluorescence intensity (TFI) of PTEC in CKD cats compared with young and geriatric normal cats, and in the DTEC of CKD cats compared with young normal cats. When histograms of individual TFI were compared, statistically significant decreases in the PTEC and DTEC of CKD cats were observed compared with young and geriatric normal cats. Concomitantly, a statistically significant increase in SABG staining was seen in CKD kidney samples compared with young normal cats. CKD cats tended to have increased SABG staining in the kidney compared with normal geriatric cats, but this did not reach statistical significance. No significant telomere shortening in liver or skin from any group was observed. Real-time quantitative telomeric repeat amplification protocol assessment of renal telomerase activity revealed comparable low levels of telomerase activity in all groups. Our results suggest that shortened telomeres and increased senescence in the kidneys of CKD cats may represent novel targets for interventional therapy.

BACKGROUND

Relapsed small cell lung cancer (SCLC) is classified into sensitive or resistant according to treatment-free interval (TFI) longer or shorter than 60 (criteria 1) or 90 (criteria 2) days. However, these criteria are based on small old studies and are inconsistent among different studies. The present study aimed at validating these criteria and assessing additional clinical parameters predictive of response rate (RR) and overall survival (OS).

METHODS

A database of six GlaxoSmithKline-sponsored trials of intravenous topotecan-based second-line chemotherapy was analysed. Validation of sensitive/resistant definition was performed on the entire dataset (631 patients), while study of additional parameters and development of prognostic model was conducted dividing the database into derivation and validation sets.

RESULTS

The association between criterion 1 or 2 and RR was confirmed. Changing TFI cut-off or adding response to first-line did not improve accuracy. In addition to TFI (P=0.007), only presence of liver metastasis (P=0.046) was found to affect the probability of objective response. TFI, age, liver metastases, performance status (PS), albumin, haemoglobin and sodium levels were identified as independent prognostic factors for OS. A prognostic model, based on these variables, was able to separate relapsed SCLC into low versus high risk categories (median OS 41.4 versus 20.0 weeks).

CONCLUSIONS

This study confirms the value of standard criteria for relapsed SCLC outcome prediction. Patients with TFI<60 days are refractory to second-line chemotherapy and have poor OS. Patients with liver metastasis and/or PS2 and/or low albumin, regardless of TFI, have similarly poor outcome.

Fibroblast growth factor 2 (FGF-2) immunoreactivity (IR) was examined in the ependyma and choroid plexus (CP) of lateral and third ventricles in normal adult rats, as well as in response to transient forebrain ischemia (TFI) and exogenous FGF-2 delivered intraventricularly for several days by osmotic pump. Similar patterns of FGF-2 IR were seen in the CP epithelia of both lateral and third ventricles, as well as in ependymal cells of the third ventricle and along lateral sides of the lateral ventricles. Consistent staining was seen along the apical aspect of epithelial cells facing the cerebrospinal fluid (CSF). Cytoplasmic staining was seen in the absence of ischemia, and was dramatically reduced in response to TFI. FGF-2 treatment followed by TFI resulted in sustained FGF-2 IR within CP and ependymal cells, supporting the idea that these tissues are involved in synthesis and secretion of growth factors into the CSF. In contrast, along the medial sides of the lateral ventricles, adjacent to brain structures such as the hippocampus, consistent staining was seen along the basal aspect of the ependymal cells. We propose that at least some regions of ependyma may function to transport molecules such as FGF-2 directly into the underlying brain parenchyma.

The luteinizing hormone receptor (LHR), a member of the G protein-coupled, seven transmembrane receptor family, is essential for normal sexual development and reproductive function. LHR are expressed primarily in the gonads, but also are found in non-gonadal and cancer tissues. LH acts through LH receptors in Leydig cells to maintain general metabolic processes and steroidogenic enzymes, and in the ovary enhances follicular development and steroidogenesis in granulosa and luteal cells. The major transcriptional start sites of the LHR gene are located within the 176bp promoter domain. In the rat, the LHR gene is constitutively inhibited by upstream sequences (-176/-2056bp) in several cell systems, while in the human only a minor inhibitory effect was observed in JAR and HeLa cells (>20%). The TATA-less human promoter is driven by Sp1 and Sp3 transactivators that bind to two Sp1 domains at -79bp [Sp1(I)] and -119bp [Sp1(II)] (from ATG) with additive effects. An imperfect estrogen receptor half-site response element direct-repeat within the LHR promoter is an inhibitory locus. Endogenous orphan receptors, EAR2 and EAR3/COUP-TFI, bind this motif and repress promoter activity by 70%. TR4 also binds this motif and stimulates promoter activity (up to 2.5-fold). This is reversed by coexpression of EAR2 or EAR3/COUP-TFI through competitive binding to this site. Comparative studies of hDR and rDR orphan receptors binding and function revealed sequence-specific requirements. The A/C mismatch between hDR and rDR is responsible for the lack of TR4 binding and function in the rat. The G 3'-adjacent to the hDR core is important for EAR2/EAR3-COUP-TFI high-affinity binding. The Sp1-1 site is critical for EAR3/COUP-TFI repression, with minor participation for EAR2, and is not involved in the TR4 effect. Interaction of EAR3/COUP-TFI with Sp1 perturbs association of TFIIB with Sp1, independently of HDACs, and caused impairment of LHR transcription. Other aspect of control is through HDAC/mSin3A mechanism. Inhibition of HDACs by TSA increases LHR promoter activity in JAR cells (40-fold), association of acetylated H3/H4 with the LHR promoter, recruitment of Pol II to the promoter, and LHR mRNA levels. A multiprotein complex is recruited to the hLHR promoter via interaction with Sp1/Sp3: HDACs dock directly to Sp1-1 bound DNA and indirectly to Sp3-1 bound DNA through RbAp48, while mSin3A interacts HDACs and potentiates HDAC1-mediated repression. Our studies have demonstrated that orphan receptor-ERE complexes, and the HDAC1-HDAC2-mSin3A complex have important roles in the regulation of LHR gene transcription by interaction with Sp1/Sp3, and by region-specific changes in histone acetylation and Pol II recruitment within the LHR promoter.

Due to rapidly aging human populations, frailty has become an essential concept, as it identifies older people who have higher risk of adverse outcomes, such as disability, institutionalization, lower quality of life, and premature death. The Tilburg Frailty Indicator (TFI) is a user-friendly questionnaire based on a multidimensional approach to frailty, assessing physical, psychologic, and social aspects of human functioning. This review aims to explore the efficiency of the TFI in assessing frailty as a means to carry out research into the antecedents and consequences of frailty, and its use both in daily practice and for future intervention studies. Using a multidimensional approach to frailty, in contexts where health care professionals or researchers may have no time to interview or examine the client, we recommend employing the TFI because there is robust evidence of its reliability and validity and it is easy and quick to administer. More studies are needed to establish whether the TFI is suitable for intervention studies not only in the community, but also for specific groups such as patients in the hospital or admitted to an emergency department. We conclude that it is important to not only determine the deficits that frail older people may have, but also to assess their balancing strengths and resources. In order to be able to meet the individual needs of frail older persons, traditional and often fragmented elderly care should be developed toward a more proactive elderly care, in which frail older persons and their informal network are in charge.

The objectives of this study were to compare how different frailty measures (Frailty Phenotype/FP, Groningen Frailty Indicator/GFI and Tilburg Frailty Indicator/TFI) predict short-term adverse outcomes. Secondarily, adopting a multidimensional approach to frailty (integral conceptual model-TFI), this study aims to compare how physical, psychological and social frailty predict the outcomes. A longitudinal study was carried out with 95 community-dwelling elderly. Participants were assessed at baseline for frailty, determinants of frailty, and adverse outcomes (healthcare utilization, quality of life, disability in basic and instrumental activities of daily living/ADL and IADL). Ten months later the outcomes were assessed again. Frailty was associated with specific healthcare utilization indicators: the FP with a greater utilization of informal care; GFI with an increased contact with healthcare professionals; and TFI with a higher amount of contacts with a general practitioner. After controlling for the effect of life-course determinants, comorbidity and adverse outcome at baseline, GFI predicted IADL disability and TFI predicted quality of life. The effect of the FP on the outcomes was not significant, when compared with the other measures. However, when comparing TFI's domains, the physical domain was the most significant predictor of the outcomes, even explaining part of the variance of ADL disability. Frailty at baseline was associated with adverse outcomes at follow-up. However, the relationship of each frailty measure (FP, GFI and TFI) with the outcomes was different. In spite of the role of psychological frailty, TFI's physical domain was the determinant factor for predicting disability and most of the quality of life.

BACKGROUND

In the last decade, studies on frailty have become increasingly frequent in the literature on aging, and also the number of available questionnaires regarding frailty has increased over the years. Therefore, the choice of which questionnaire to use is becoming more difficult.

OBJECTIVE

The aim of this study was to assess the psychometric properties of the Polish version of the Tilburg Frailty Indicator (TFI), an instrument that identifies frailty in the elderly population.

METHODS

Setting, and Participants. The study was carried out in a community-based setting in Wrocław, Poland. Nurses and doctors (general practitioners) administered the TFI in primary care facilities. Participants included a sample of 212 community dwelling elderly aged 60 or older (mean age:70.6 SD≥7.16).

METHODS

The validation (assessment of face validity, content validity) was carried out in accordance with the literature. The Tilburg Frailty Indicator (TFI) consists of two different parts. One part addresses the potential determinants of frailty and the other specifically addresses the components of frailty, covering its physical, psychological and social domains. Scale reliability was estimated using two methods: Cronbach's alpha, measuring the scale's internal consistency, and the test-retest method, determining the scale's absolute stability. To assess test-retest reliability, the same group was re-interviewed by the same observer within 10-14 days of the first interview.

RESULTS

The test-retest reliability showed a high level of agreement for all items of the instrument, with values ranging from 96 to 100%. The Cronbach's Alpha internal consistency was 0.74.

CONCLUSIONS

The Polish version of the TFI proved to be a valid and reproducible tool for assessment of Frailty Syndrome for the Polish population. We would recommend to be used as the screening tool to assess frailty.

This study aims to assess the reliability, construct validity (convergent/divergent), and criterion validity of the Italian version of the Tilburg Frailty Indicator (TFI). The TFI is a self-report questionnaire for screening frailty in older adults. Two hundred and sixty-seven community-dwelling older adults were involved. Psychometric properties were analyzed using validated instruments. Adverse outcomes such as disability, falls, and visits to a general practitioner were detected. Participants were mainly women (59.9%), with a mean age of 73.4 years (SD = 6.0). Internal consistency reliability was acceptable. Construct validity was good, since each item of the TFI correlated as expected with corresponding frailty measures. Convergent and divergent validity were adequate for all the domains of the TFI. Criterion validity was excellent for disability and mediocre for the other two outcomes. This study supports the validity of the Italian TFI and offers to clinicians and scientists a multidimensional instrument for identifying frail individuals in the Italian context.

Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are members of the steroid/thyroid hormone receptor superfamily. We have shown that two homologous COUP-TF genes, COUP-TFI and COUP-TFII, are expressed in developing mouse retina with a unique gradient along the dorsal-ventral axis. In this work, we aimed to characterize the detailed expression patterns of COUP-TFs in mature retina. Their functions in retinal progenitor cell differentiation into subtypes of mature retinal cells were also examined. Immunostaining of frozen mouse retinal sections with antibodies against COUP-TFs and markers for retinal subtypes revealed that COUP-TFI and -TFII are expressed in amacrine cells, especially in a glycinergic subtype in mature mouse retina. Forced expression of COUP-TFI and -TFII in mouse retinal explant culture by retrovirus-mediated gene transfer promoted amacrine and cone photoreceptor cell differentiation, whereas that of rod photoreceptors decreased. Cell proliferation and apoptosis were not affected by the perturbation of COUP-TFI and -TFII expression levels. Using the Y79 retinoblastoma cell line, we observed that COUP-TFI and -TFII suppressed the transcriptional activation of the Nrl gene. We then analyzed one another member of COUP-TF transcription factors, COUP-TFgamma, whose structure is relatively distant from those of COUP-TFI and -TFII. It is expressed mainly in horizontal cells and has weak activity in inducing amacrine cells when COUP-TFgamma was ectopically expressed in retinal explants. In summary, we found that COUP-TFI and -TFII play roles in amacrine cell differentiation, and COUP-TFgamma has distinct expression pattern and roles during retinal development.

The chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) are orphan receptors involved in regulation of embryonic development and neuronal cell fate determination. We identified a target of COUP-TF involved in cell proliferation and cell differentiation. Using reporter assays, footprint analysis, and electrophoretic mobility shift assays, we showed that a nuclear hormone-responsive element located at -841/-800 nt of the mouse Na(+)/H(+) exchanger (NHE) promoter binds COUP-TF with enhancer activity. Mutation at -829/-824 nt (and secondarily at -837/-833) prevents COUP binding and activation of the NHE promoter. In vivo expression of COUP isoforms in NIH 3T3 or CV1 cells transactivates from the nuclear hormone-responsive element and from the entire NHE1 promoter. Transactivation is greater for COUP-TFII, is increased for either COUP isoform by the presence of high serum concentrations, and is greatly reduced by mutations preventing COUP binding. In vivo COUP expression in NIH 3T3 cells results in increased synthesis of NHE. Expression of COUP-TFII induced by either retinoic acid or dimethyl sulfoxide in differentiating P19 cells increases NHE expression. The results show that COUP-TF regulates expression of the NHE and provide a mechanism that may be important in physiological and pathological situations linked to its upregulation.