OBJECTIVE

We sought to clarify the mechanisms of backup force for right coronary artery intervention.

BACKGROUND

Backup force of a guiding catheter is important for successful percutaneous coronary intervention (PCI); however, little attention has been given to its mechanism.

RESULTS

Backup force of guiding catheters was measured in an arterial tree model. Judkins R, Amplatz L and Ikari R had greater backup force in the transfemoral intervention (TFI) than the transradial intervention (TRI). The primary attachment site of the catheter was the aortic arch in TFI, but it was the brachiocephalic artery in right TRI. This may be a major reason for the different backup force because generation of backup force is governed by the mechanics of the catheter at the attachment site. The Amplatz L and Ikari R had stronger backup force than the Judkins R both in TFI and in TRI because a slight backward motion of the catheter due to device advancement changed the primary attachment site to the reverse side of the aorta or sinus of Valsalva. The primary attachment site of the Ikari L at the power position was the reverse side of the aorta both in TFI and TRI, which was different from other catheters.

CONCLUSIONS

The primary attachment site of the catheter had great impact on the backup force in right coronary interventions. An understanding of the mechanism by which the guiding catheter works in TRI and TFI may help in choosing an appropriate approach site.

OBJECTIVE

Scanning laser vibrometry is a non-invasive method of accurately measuring the vibratory characteristics of oscillating objects. The aim of this study was to observe, using a scanning laser vibrometer (SLV), the vibration patterns of dental ultrasonic scaler tips and to assess the effects of water flow rate and power setting on these patterns whilst operating the tips in an unloaded environment.

METHODS

A 30kHz ultrasonic scaler (TFI-10, Dentsply) was fixed in position and a laser beam from the SLV was focused onto the tip. The laser, guided by a virtual measurement grid, was scanned over the oscillating tip surface. Scans were taken with the laser beam perpendicular to the long axis of the front face of the tip.

RESULTS

Oscillation frequencies and the displacement amplitude at the unconstrained end of the tip were measured for various power/water settings. Vibration nodal positions were recorded for the various settings and were found to occur approximately 4mm from the free end of the tip. At low and medium power settings, tip displacement amplitude was reduced by increased water flow. At high power settings, combined with a high flow rate, the water leaves the body of the instrument as a jet. This left the tip relatively unconstrained, allowing it to oscillate at increased displacement amplitudes.

CONCLUSIONS

This study shows that the SLV is able to accurately characterise the movement of oscillating ultrasonic scaler tips. The tips are affected by power setting and water flow rates.

The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily that play distinct and critical roles in vertebrate organogenesis, as demonstrated by loss-of-function COUP-TFI and/or COUP-TFII mutant mice. Although COUP-TFs are expressed in a wide range of tissues in adults, little is known about their functions at later stages of development or in organism homeostasis. COUP-TFs are expressed in cancer cell lines of various origins and increasing studies suggest they play roles in cell fate determination and, potentially, in cancer progression. Nevertheless, the exact roles of COUP-TFs in these processes remain unclear and even controversial. In this review, we report both in vitro and in vivo data describing known and suspected actions of COUP-TFs that suggest that these factors are involved in modification of the phenotype of cancer cells, notably of epithelial origin.

BACKGROUND

The tear function index (TFI) has been shown to be of value in the diagnosis of patients suffering from Sjögren's syndrome. It is dependent, however, on introducing into the conjunctival fornix the correct concentration of fluorescein in at least one and a half times the normal tear volume. The stimulus and effect of this added volume on the tear dynamics is likely to vary between individuals. These factors, together with the method of performing the test, limit its general applicability.

OBJECTIVE

To devise a method of performing the TFI with less variability and more general applicability. To present a theoretical and in vitro assessment of the dynamics of the TFI.

METHODS

The study was divided into three parts. The first part was to compare the results obtained using a prepared strip containing 1.3 microl of 0.5% fluorescein with the introduction of the same amount of fluorescein as a drop. The second part was to compare the results obtained with prepared strips with the standard method of performing the TFI, both with and without topical anaesthetic. The third part was an in vitro study of the rate of flow of graded volumes on a filter paper strip. 42 subjects with a diagnosis of Sjögren's syndrome according to the European criteria and 126 without Sjögren's syndrome were included.

RESULTS

There was no significant difference between the results obtained with a prepared strip and the introduction of 1.3 microl into the eye before performing the Schirmer's test and <em>TFI</em> (0.1<p<0.93). There was, likewise, no significant difference between using the prepared strips and the standard method of performing the <em>TFI</em> (0.36<p<0.93). There was, however, less interocular difference (p=0.01) and variability (p=0.001) using the prepared strips than using a drop of fluorescein. Patients with Sjögren's syndrome had mean <em>TFI</em>s of 11.7 and 8.61 with upper 95% confidence values of 15 and 12 without and with topical anaesthetic, respectively. The theoretical calculation of the <em>TFI</em> was similar to the observed values. The in vitro results allow the filter paper to be removed from the eye at any interval and to estimate the volume of tears that the filter paper was in contact with.

CONCLUSIONS

The proposed method of performing the TFI is easy to perform, reliable, and therefore has general applicability for primary care and general practitioners. It allows the rapid identification of subjects who may be suffering from Sjögren's syndrome.

BACKGROUND

Frailty can lead towards serious adverse consequences, such as disability. With regard to prevention valid screening instruments are needed to identify frail older people. The aim was to evaluate and compare the psychometric properties of three screening instruments: the Groningen Frailty Indicator (GFI), the Tilburg Frailty Indicator (TFI) and the Sherbrooke Postal Questionnaire (SPQ). For validation purposes the Groningen Activity Restriction Scale (GARS) was added.

METHODS

A questionnaire was sent to 687 older people >> or = 70 years). (1) Agreement between instruments, (2) internal consistency, (3) cumulative scalability according to Mokken scale analysis and (4) construct validity were evaluated.

RESULTS

The response rate was 77%. Prevalence estimates of frailty ranged from 40% to 59%. The highest agreement was found between the GFI and TFI (Cohen's kappa = 0.74). Cronbach's alpha for the GFI, TFI and SPQ was 0.73, 0.79 and 0.26, respectively. The scalability of the three instruments was inadequate (Loevinger's H: 0.28, 0.30 and 0.09 for GFI, TFI and SPQ, respectively). Frailty scores correlated significantly with each other and with the GARS scores.

CONCLUSIONS

Especially the GFI and TFI seem to be useful to identify frail older people. Further research regarding their predictive validity is still needed.

Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second-line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment-free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first-line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate.

BACKGROUND

Mexican Americans are at an increased risk of both thyroid dysfunction and metabolic syndrome (MS). Thus it is conceivable that some components of the MS may be associated with the risk of thyroid dysfunction in these individuals. Our objective was to investigate and replicate the potential association of MS traits with thyroid dysfunction in Mexican Americans.

METHODS

We conducted association testing for 18 MS traits in two large studies on Mexican Americans - the San Antonio Family Heart Study (SAFHS) and the National Health and Nutrition Examination Survey (NHANES) 2007-10. A total of 907 participants from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007-10 were included in this study. The outcome measures were prevalence of clinical and subclinical hypothyroidism and thyroid function index (TFI) - a measure of thyroid function. For the SAFHS, we used polygenic regression analyses with multiple covariates to test associations in setting of family studies. For the NHANES 2007-10, we corrected for the survey design variables as needed for association analyses in survey data. In both datasets, we corrected for age, sex and their linear and quadratic interactions.

RESULTS

TFI was an accurate indicator of clinical thyroid status (area under the receiver-operating-characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and NHANES 2007-10. Of the 18 MS traits, waist circumference (WC) showed the most consistent association with TFI in both studies independently of age, sex and body mass index (BMI). In the SAFHS and NHANES 2007-10 datasets, each standard deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p < 0.001) unit increase in the TFI, respectively. In a series of polygenic and linear regression models, central obesity (defined as WC ≥ 102 cm in men and ≥88 cm in women) was associated with clinical and subclinical hypothyroidism independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated prevalence of hypothyroidism was consistently high in those with central obesity, especially below 45y of age.

CONCLUSIONS

WC independently associates with increased risk of thyroid dysfunction. Use of WC to identify Mexican American subjects at high risk of thyroid dysfunction should be investigated in future studies.

Abstract Purine analogs are highly effective in hairy cell leukemia (HCL) with response rates of 85%, but with many late relapses. We have retrospectively reviewed the clinical data from 107 patients treated with pentostatin (n = 27) or cladribine (n = 80), to investigate the long-term efficacy and to identify factors associated with the treatment-free interval (TFI). Complete remission and minimal residual disease (MRD) rates were similar in both groups. Median TFI was shorter (95 vs. 144 months) in the pentostatin group, although the difference was not significant (p = 0.476). MRD+ patients had shorter TFI than MRD- patients (97 months vs. not reached, p < 0.049). A hemoglobin level < 10 g/dL predicted for a shorter TFI only in the pentostatin group. Quality of response and number of hairy cells in the bone marrow are independent risk factors of treatment failure. The relationship between MRD+ and shorter TFI makes it of special interest to explore consolidation therapy with monoclonal antibodies to achieve durable responses.

Chronic lymphocytic leukemia (CLL) follows a variable clinical course which is difficult to predict at diagnosis. We assessed somatic mutation (SHM) status, CD38 and ZAP-70 expression in 87 patients (49 male, 38 female) with stage A CLL and known cytogenetic profile to compare their role in predicting disease progression, which was assessed by the treatment free interval (TFI) from diagnosis. Sixty (69%) patients were SHM+, 24 (28%) were CD38+ and ten (12%) were ZAP-70+. The median TFI for: (i) SHM + versus SHM- patients was 124 versus 26 months; hazard ratio (HR) = 3.6 [95% confidence interval (CI) = 1.8 - 7.3; P = 0.001]: (ii) CD38- versus CD38+ patients was 120 versus 34 months; HR = 2.4 (95% CI = 1.4 - 5.3; P = 0.02); and (iii) ZAP70- versus ZAP70+ was 120 versus 16 months; HR = 3.4 (95% CI = 1.4 - 8.7; P = 0.01). SHM status and CD38 retained prognostic significance on multivariate analysis whereas ZAP-70 did not. We conclude that ZAP-70 analysis does not provide additional prognostic information in this group of patients.

Testicular biopsies and hormone studies have been carried out on 229 children with unilateral (181) or bilateral (48) undescended ectopic obstructed testes not associated with other pathologic conditions. With regard to the histologic lesions, the obstructed testes may be classified into four types: (1) testes with minimal lesions (40.1%), showing slight reduction in both mean tubular diameter (MTD) and tubular fertility index (TFI); (2) testes with marked germinal hypoplasia (33.6%), showing slight or marked reduction in MTD and marked reduction in TFI; (3) testes with diffuse tubular hypoplasia (19.1%), showing severe reduction in MTD, marked or severe germinal hypoplasia, and normal or decreased Sertoli cell number per transverse tubular section (SCI); and (4) testes with Sertoli cell hyperplasia (7.2%), showing slightly decreased MTD, marked or severe germinal hypoplasia, and marked increased in SCI. These lesions are similar to those found in cryptorchid testes, although the proportion of testes with type III and IV lesions (the most severe) is lower than in cryptorchid testes. Hormone assays revealed normal basal gonadotropin and testosterone levels. The response of gonadotropins to gonadotropin-releasing hormone stimulation and the response of testosterone to human chorionic gonadotropin stimulation were normal or slightly reduced.

BACKGROUND

A transient increase in gonadotropins and testosterone during mini-puberty causes gonocytes to differentiate into Ad spermatogonia, which establish male germ cell memory and male-specific DNA methylation pathways. Over half of patients with unilateral cryptorchidism and the majority of patients with bilateral cryptorchidism display an abnormal spermiogram, which indicates that unilateral cryptorchidism is a bilateral disease; therefore, it represents a serious andrological problem. The aim of this study was to evaluate relationships between hormonal parameters and testicular biopsy findings in boys with cryptorchidism.

METHODS

Seventy-one boys (median age 15 months; range 7-65 months) who underwent orchidopexy (24% had bilateral cryptorchidism) were tested for serum LH, FSH, and inhibin B. With ipsilateral testis biopsy histology, we determined the tubular fertility index (TFI), Ad spermatogonia counts, and Ad/tubular index (Ad/T). We compared age groups (<18 vs. >18 months old); groups with and without Ad spermatogonia; groups with unilateral and bilateral cryptorchidism; and extreme groups with high infertility risk (HIR; n = 12; TFI <0.2; Ad/T = 0) and low infertility risk (LIR; n = 9; TFI >0.9; Ad/T>0.02).

RESULTS

Of the specimens, 38% had no Ad spermatogonia. Age was significantly negatively correlated with TFI and Ad/T, but positively correlated with FSH. Median LH values were significantly higher in LIR than in HIR groups. Unilateral and bilateral cryptorchidism showed similar TFI, Ad/T, and hormone concentrations. The areas under ROC curves for FSH, LH, and inhibin B (0.66, 0.601, and 0.599, respectively) showed low diagnostic value for predicting HIR (no Ad spermatogonia).

CONCLUSIONS

Our observation of lower plasma LH levels in the group with the most pronounced testicular pathology was the opposite of what we would have expected if testicular pathological changes were caused by a primary gonadal defect. Therefore, low plasma LH levels in the HIR group confirmed the notion that this group of patients with cryptorchidism had hypogonadotropic hypogonadism. The estimated incidence of defective mini-puberty in boys with cryptorchidism could be as high as 50%. Testicular biopsies from boys with cryptorchidism lacked Ad spermatogonia. Fertility parameters worsened with age. Significantly lower basal LH in the HIR group indicated hypogonadotropic hypogonadism. Serum hormone levels could not predict histological biopsy findings.

OBJECTIVE

While primary treatment for high-grade serous ovarian cancer tends to be uniform - maximal debulking and platinum/taxane adjuvant chemotherapy - there is little standardization of treatment in the recurrent setting beyond the exhaustive use of platinum therapies. Using secondary data from multiple centers participating in the Cancer Genome Atlas study (TCGA), we seek to characterize clinical features, timing and serial response data to provide empirical evidence for treatment expectations in the recurrent setting.

METHODS

We conducted a retrospective survival analysis of TCGA study primary and secondary patient chemotherapy regimens by characterizing the dynamics of 1119 lines of therapy comprising the treatment of 461 high-grade serous ovarian cancer patients. All patients with post-surgical drug therapy information from the TCGA database were included in this study.

RESULTS

A complete response to adjuvant therapy led to longer overall survival, but did not affect treatment free intervals (TFIs) after relapse of disease. A strong predictor of the TFI on the next treatment regimen was the previous TFI with a decaying effect. The number of previous treatments, of platinum treatments, and the length of time from surgery all have an exponentially decreasing effect on TFI. Re-treatment times appear to cluster at predictable times following surgery.

CONCLUSIONS

While patients experience a consistent reduction in TFI with increasing re-treatment, the initial adjuvant interval is unrelated to later interval lengths. Platinum re-treatment remained an effective option in patients typically thought to be platinum resistant and the timing of monitoring visits may drive overall re-treatment patterns.

Partial nerve lesions with a varying degree of retained function and often a painful neuroma pose a dilemma for the clinician. Surgical treatment of partial nerve lesion is perilous because of possible damage to intact axons and subsequent loss of retained function. We present a new rat model of a partial nerve lesion, allowing further study to improve treatment for this condition. A partial (50%) lesion of the tibial portion of the rat sciatic nerve was created and compared to standard crush and neurectomy control lesions. The extent of lost function and the progress of postoperative recovery following the three lesions were compared using serial walking track analyses and end-point muscle weight ratios for atrophy as outcome measures. All groups had tibial functional indices (TFI) significantly different from one another after 1 week. TFIs for the crush group returned to normal by 4 weeks, whereas the neurectomy group showed no recovery. The partial lesion group gradually improved, reaching a plateau of 44% by 7 weeks. Gastrocnemius muscle weight ratios for the partial, crush, and neurectomy lesions at 9 weeks were 0.63, 0.87, and 0.32, respectively. There was a strong correlation between the TFI and muscle weight ratios (r(2) = 0.89; P < 0.001) suggesting that these outcome measures are highly predictive of function. In conclusion, the partial lesion showed a gradual but incomplete functional recovery with a complementary degree of muscle atrophy. The model may prove useful in the evaluation of proposed treatments for partial nerve lesions and the associated painful state.

The standard postoperative chemotherapy for epithelial ovarian cancer is a combination therapy including platinum and taxanes. The aim this study was to investigate the degree of platinum sensitivity in patients with relapsed epithelial ovarian cancer according to the treatment-free interval (TFI) and the histological tumor type. The medical records of 405 patients diagnosed with stage III/IV ovarian cancer, including 107 patients who relapsed after attaining a clinical complete response with first-line treatment, were retrospectively reviewed. The degree of platinum sensitivity was assessed by comparing the progression-free survival (PFS) following the second-line treatment. In patients with serous/endometrioid adenocarcinoma who were treated with platinum following relapse, there were significant differences in the PFS between the following groups of patients: those who relapsed within 6 months and those who relapsed between 6 and 12 months; those who relapsed between 6 and 12 months and those who relapsed between 12 and 18 months; and those who relapsed between 12 and 18 months and those who relapsed after 18 months. By contrast, in patients with clear cell/mucinous adenocarcinoma who were treated with platinum following a relapse, there were no significant differences in the PFS between patients who relapsed within 6 months and those who relapsed between 6 and 12 months, while there were significant differences in the PFS between those who relapsed between 6 and 12 months and those who relapsed after 12 months. With regard to the patients who relapsed after 12 months, the PFS of those with clear cell/mucinous adenocarcinoma was significantly shorter compared with the PFS of those with serous/endometrioid adenocarcinoma. Therefore, we considered it justified to classify patients with clear cell/mucinous adenocarcinoma who relapsed within 12 months as platinum-resistant and those who relapsed after 12 months as platinum-sensitive.

BACKGROUND

TNFR2-Fc and IL-1ra-Fc are recombinant cytokine ligands that target TNF and IL-1. TNFR2-Fc-IL-1ra, a dual-domain agent that incorporates both ligands, allows bifunctional binding of IL-1 receptors and TNF. This study was designed to characterize (99m)Tc-labeled forms of these ligands, (99m)Tc-IL-1ra-Fc (IF), (99m)Tc-TNFR2-Fc (TF), and (99m)Tc-TNFR2-Fc-IL-1ra (TFI), for inflammation imaging.

METHODS

The cytokine ligands were labeled with (99m)Tc by a direct approach via 2-iminothiolane (2-IT) reduction at various 2-IT/protein molar ratios. In vivo inflammation targeting studies were carried out in a mouse ear edema model created by topical application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the right ear of ICR mice.

RESULTS

Radiolabeling yields increased with increasing amounts of 2-IT. When the 2-IT/protein ratio reached 1000, the radiolabeling yield was greater than 90% without significant colloid production. TPA-treated ears showed high radioligand uptake, which was clearly detected by SPECT and autoradiographic imaging. The activities (%ID/g) in the inflamed and control ears at 3h after injection were 2.76 ± 0.20 vs. 0.69 ± 0.12 for IF, 5.86 ± 0.40 vs. 2.86 ± 0.61 for TF, and 7.61 ± 0.86 vs. 1.99 ± 0.31 for TFI (P<0.05 vs. controls). TFI showed significantly higher uptake in the inflamed ears compared to TF and IF (P<0.05). Blocking study results indicated specificity of radioligand binding with decreased radioactive uptake in the inflamed ears. Western blotting and ELISA analysis further confirmed a high expression of IL-1β and TNF-α in the inflamed ears.

CONCLUSIONS

(99m)Tc-labeled cytokine ligands are a promising approach for detecting and understanding the inflammatory process. TFI may be more useful than the single-domain ligands for noninvasive detection of inflammatory sites.

We have shown previously that the PTH/PTHrP (PTH-related peptide) receptor mRNA becomes expressed very early in murine embryogenesis, i.e. during the formation of extraembryonic endoderm. Retinoic Acid (RA) is a potent inducer of extraembryonic endoderm formation and PTH/PTHrP-receptor expression in embryonal carcinoma (EC) and embryonal stem (ES) cells. Using the P19 EC cell line, we have characterized promoter elements of the murine PTH/PTHrP-receptor gene that are involved in this RA-induced expression. The data show that RA-induced expression of the PTH/ PTHrP-receptor gene is mediated by the downstream P2 promoter. Analysis of promoter reporter constructs in transiently transfected P19 cells treated with RA identified an enhancer region between nucleotides -2714 and -2702 upstream of the P2 transcription start site that is involved in the RA effect. This region matches a consensus hormone response element consisting of a direct repeat with an interspacing of 1 bp (R-DR1). The R-DR1 efficiently binds retinoic acid receptor-alpha (RARalpha)-retinoid X receptor-alpha (RXRalpha) and chicken ovalbumin upstream promoter (COUP)-transcription factor I (TFI)-RXRalpha heterodimers and RXRalpha and COUP-TFI homodimers in a bandshift assay using extracts of transiently transfected COS-7 cells. RA differentiation of P19 EC cells strongly increases protein binding to the R-DR1 in a band-shift assay. This is caused by increased expression of RXR (alpha, beta, or gamma) and by the induction of expression of RARbeta and COUP TFI/TFII, which bind to the R-DR1 as shown by supershifting antibodies. The presence of RXR (alpha, beta, or gamma) in the complexes binding to the R-DR1 suggests that RXR homodimers are involved in RA-induced expression of the PTH/PTHrP-receptor gene. The importance of the R-DR1 for RA-induced expression of PTH/ PTHrP-receptor was shown by an inactivating mutation of the R-DR1, which severely impairs RA-induced expression of PTH/PTHrP-receptor promoter reporter constructs. Since this mutation does not completely abolish RA-induced expression of PTH/PTHrP-receptor promoter reporter constructs, sequences other than the R-DR1 might also be involved in the RA effect. Finally, we show that the RA-responsive promoter region is also able to induce expression of a reporter gene in extraembryonic endoderm of 7.5 day-old transgenic mouse embryos.

Exposure of embryos to an excess of retinoic acid (RA) modifies the spatio-temporal pattern of expression of developmental genes. RA regulates the expression of target genes through binding of the retinoid nuclear receptors (RARs and RXRs), as heterodimers, to regulatory cis-acting elements. COUP-TF factors, which are able to dimerize with the RXRs and to compete with the retinoid receptors for their DNA binding sites, are suspected to modulate the retinoid signal transduction pathway. Therefore, COUP-TF factors may be involved in the regulation of the expression of developmental genes and/or in the modifications induced by an excess of RA in the expression of these genes. The aim of this work is to assess whether RA-induced modifications in the expression of Krox-20 and Hox genes correlate with alterations of the expression of COUP-TF genes. In addition to spatial modifications in the expression patterns of Krox-20 and Hox genes, we report here an upregulation of the expression level of COUP-TFI after RA exposure. However, this abnormality did not spatially overlap with the modifications observed in the expression of Krox-20 and Hox genes. These data suggest an involvement of COUP-TFI in the generation of RA-induced abnormalities, but do not support the hypothesis of an involvement of this factor in the regulation of the expression of Hox or Krox-20 genes.

The aim of this investigation was to determine if cavitation occurred around dental ultrasonic scalers and to estimate the amount of cavitation occurring. Three styles of tip (3 x TFI-10, 3 x TFI-3, 3 x TFI-1) were used, in conjunction with a Cavitron SPS ultrasonic generator (Dentsply, USA), to insonate terephthalic acid solution. The hydroxyl radical, [*OH], concentration, produced due to cavitation from the scaler tips, was monitored by fluorescence spectroscopy. Cavitational activity was enhanced at higher power settings and at longer operating times. The tip dimensions and geometry as well as the generator power setting are both important factors that affect the production of cavitation.

A stochastic risk model was developed to estimate the time elapsed before overcrowding (TOC) or feed interruption (TFI) emerged on the swine premises under movement restrictions during a classical swine fever (CSF) outbreak in Indiana, USA. Nursery (19 to 65 days of age) and grow-to-finish (40 to 165 days of age) pork production operations were modelled separately. Overcrowding was defined as the total weight of pigs on premises exceeding 100% to 115% of the maximum capacity of the premises, which was computed as the total weight of the pigs at harvest/transition age. Algorithms were developed to estimate age-specific weight of the pigs on premises and to compare the daily total weight of the pigs with the threshold weight defining overcrowding to flag the time when the total weight exceeded the threshold (i.e. when overcrowding occurred). To estimate TFI, an algorithm was constructed to model a swine producer's decision to discontinue feed supply by incorporating the assumptions that a longer estimated epidemic duration, a longer time interval between the age of pigs at the onset of the outbreak and the harvest/transition age, or a longer progression of an ongoing outbreak would increase the probability of a producer's decision to discontinue the feed supply. Adverse animal welfare conditions were modelled to emerge shortly after an interruption of feed supply. Simulations were run with 100 000 iterations each for a 365-day period. Overcrowding occurred in all simulated iterations, and feed interruption occurred in 30% of the iterations. The median (5th and 95th percentiles) TOC was 24 days (10, 43) in nursery operations and 78 days (26, 134) in grow-to-finish operations. Most feed interruptions, if they emerged, occurred within 15 days of an outbreak. The median (5th and 95th percentiles) time at which either overcrowding or feed interruption emerged was 19 days (4, 42) in nursery and 57 days (4, 130) in grow-to-finish operations. The study findings suggest that overcrowding and feed interruption could emerge early during a CSF outbreak among swine premises under movement restrictions. The outputs derived from the risk model could be used to estimate and evaluate associated mitigation strategies for alleviating adverse animal welfare conditions resulting from movement restrictions.

Although neuronal death has been studied in experimental models of ischemia, the precise mechanisms regulating cell death remain unclear. Furthermore, the timing and pattern of neuronal death in human stroke has not been extensively studied. To further our understanding of ischemia-induced neuronal death, we examined the temporal profile of histochemical and morphologic characteristics of hippocampal neuronal death following experimental forebrain ischemia and compared these findings to human brain specimens obtained from subjects suffering cerebral infarction. Transient forebrain ischemia (TFI) was induced in normothermic adult rats by bilateral carotid artery occlusion combined with hypotension. Animals were sacrificed at 6, 12, 18, 24, 48, and 72 h and 7, 14, and 28 days following ischemia (n = 4 at each time point). Experimental tissue was analyzed using light and electron microscopy as well as TUNEL histochemistry. A total of 27 human brain specimens with neuropathological confirmation of ischemic damage and appropriate controls were also examined using light microscopy and TUNEL histochemistry. Dense TUNEL staining in hippocampal CA-1 neurons was present at 48 and 72 h following experimental ischemia. Prior to these times, little or no nuclear staining was noted and after 72 h nuclear staining diminished rapidly. Ultrastructural findings at these time points demonstrated many features similar to those seen in cells undergoing apoptosis, such as cell shrinkage with increased electron density, chromatin condensation with formation of heterochromatin, intact plasma membranes, and intact intracellular organelles. In a similar fashion, human stroke specimens during the subacute period showed dense nuclear TUNEL staining in penumbral neurons, whereas in the acute or chronic stages little or no staining was noted. Our results demonstrate that the timing of morphologic changes and TUNEL histochemistry following human stroke resembles that observed in experimental TFI. Furthermore, neuronal death in both experimental ischemia and human stroke share several features characteristic of apoptotic cell death.

BACKGROUND

Data are limited regarding the clinical results of transradial coronary intervention (TRI) in acute myocardial infarction (AMI) complicated by cardiogenic shock.

OBJECTIVE

The aim of this study was to compare the clinical results of TRI and transfemoral coronary intervention (TFI) in AMI patients who had cardiogenic shock and underwent emergency percutaneous coronary intervention (PCI).

METHODS

Between January 1, 2006, and August 31, 2012, a total of 507 consecutive patients with AMI underwent emergency PCI within 12 hours of onset. Eighty-five patients presented with cardiogenic shock and were enrolled. Among these patients, 60 underwent TRI and 25 underwent TFI. Outcome measures included the following: major bleeding and vascular complications; major adverse cardiac or cerebrovascular events (MACCE); all-cause death; door-to-balloon time; and PCI procedural success.

RESULTS

TRI had a significantly lower rate of major bleeding and vascular complications within 30 days (6.7% vs. 28.0%; P<.05) and 1 year (log-rank P<.05) than TFI. No significant differences were observed between the two groups in the MACCE rate within 30 days (28.3% vs. 44.0%; P=.21) and 1 year (log-rank P=.06), and the all-cause death rate within 30 days (26.7% vs. 40.0%; P=.30) and 1 year (log-rank P=.09). In addition, TRI was not inferior to TFI in terms of door-to-balloon time (99.8 min vs. 110.4 min; P=.30) and PCI procedural success (95.0% vs. 96.0%; P>.99).

CONCLUSIONS

TRI is associated with fewer major bleeding and vascular complications than TFI, and it appears suitable for both low- and high-risk AMI patients, especially when AMI is complicated by cardiogenic shock.

In the scoliotic spine, torsion is generally evaluated in relation to axial rotation of the apical vertebra. In the lower limbs, the changes in torsion by age of femoral anteversion (FAV) relative to tibial torsion (TT) have been studied in dried bones, normal growing subjects and adults and subjects with osteoarthritis of the hip or the knee. This paper reports the application of real-time ultrasound to FAV and TT in normal children age 11-18 years and in scoliosis screening referrals with particular reference to how FAV relates to TT as 1) ratios, and 2) tibio-femoral index (TFI) of torsion, calculated as TT minus femoral FAV. The FAV/TT ratio findings show an abnormal normal relationship of FAV to TT both proximo-distally and in left-right asymmetry. These may express torsional abnormalities in femoral and/or tibial growth plates with left-right asynchrony suggesting the possibility of similar torsional abnormalities in vertebral end-plates and/or rib growth plates initiating the deformity of AIS. TFI of the right limb in the scoliosis girls is greater than in the normals that is interpreted as resulting from earlier skeletal maturation of FAV. FAV/TT ratios and TFI are unrelated to the spinal deformity (Cobb angle and apical vertebral rotation) except for boys where TFI is associated with apical vertebral rotation. FAV/TT ratios may be a more accurate method estimating the relationship of FAV to TT. than TFIs.

The current study aimed to adapt the Tilburg Frailty Indicator (TFI), used to assess frailty in the elderly, to the Brazilian population. Conceptual, item, and semantic equivalences were analyzed and the summary version was pre-tested. In the evaluation of conceptual equivalence, the construct for frailty adopted in Brazil demonstrated the same conceptualization as in other cultures where this condition has been investigated. All items included in the original version also showed similarity in the two cultures. High semantic equivalence was observed in the analysis of the items' referential and general meanings. The pre-test showed a high percentage of understanding of items and good acceptance of items by elderly individuals. The results suggest that the TFI version adapted to the Brazilian culture can be a useful tool for assessing health conditions in older Brazilians.