Differentiation of focal liver lesions: usefulness of parametric imaging with contrast-enhanced US.

Purpose: To evaluate whether parametric imaging with contrast material-enhanced ultrasonography (US) is superior to visual assessment for the differential diagnosis of focal liver lesions (FLLs). Materials and Methods: This study had institutional review board approval, and verbal patient informed consent was obtained. Between August 2005 and October 2008, 146 FLLs in 145 patients (63 women, 82 men; mean age, 62.5 years; age range, 22-89 years) were imaged with real-time low-mechanical-index contrast-enhanced US after a bolus injection of 2.4 mL of a second-generation contrast agent. Clips showing contrast agent uptake kinetics (including arterial, portal, and late phases) were recorded and subsequently analyzed off-line with dedicated image processing software. Analysis of the dynamic vascular patterns (DVPs) of lesions with respect to adjacent parenchyma allowed mapping DVP signatures on a single parametric image. Cine loops of contrast-enhanced US and results from parametric imaging of DVP were assessed separately by three independent off-site readers who classified each lesion as benign, malignant, or indeterminate. Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated for both techniques. Interobserver agreement (κ statistics) was determined. Results: Sensitivities for visual interpretation of cine loops for the three readers were 85.0%, 77.9%, and 87.6%, which improved significantly to 96.5%, 97.3%, and 96.5% for parametric imaging, respectively (P < .05, McNemar test), while retaining high specificity (90.9% for all three readers). Accuracy scores of parametric imaging were higher than those of conventional contrast-enhanced US for all three readers (P < .001, McNemar test). Interobserver agreement increased with DVP parametric imaging compared with conventional contrast-enhanced US (change of κ from 0.54 to 0.99). Conclusion: Parametric imaging of DVP improves diagnostic performance of contrast-enhanced US in the differentiation between malignant and benign FLLs; it also provides excellent interobserver agreement.

The p63 target HBP1 is required for skin differentiation and stratification.

Genetic experiments established that p63 is crucial for the development and maintenance of pluristratified epithelia. In the RNA interference (RNAi) screening for targets of p63 in keratinocytes, we identified the transcription factor, High Mobility Group (HMG) box protein 1 (HBP1). HBP1 is an HMG-containing repressor transiently induced during differentiation of several cell lineages. We investigated the relationship between the two factors: using RNAi, overexpression, chromatin immunoprecipitations and transient transfections with reporter constructs, we established that HBP1 is directly repressed by p63. This was further confirmed in vivo by evaluating expression in p63 knockout mice and in transgenics expressing p63 in basal keratinocytes. Consistent with these findings, expression of HBP1 increases upon differentiation of primary keratinocytes and HaCaT cells in culture, and it is higher in the upper layers of human skin. Inactivation of HBP1 by RNAi prevents differentiation of keratinocytes and stratification of organotypic skin cultures. Finally, we analyzed the keratinocyte transcriptomes after HBP1 RNAi; in addition to repression of growth-promoting genes, unexpected activation of differentiation genes was uncovered, coexisting with repression of other genes involved in epithelial cornification. Our data indicate that suppression of HBP1 is part of the growth-promoting strategy of p63 in the lower layers of epidermis and that HBP1 temporally coordinates expression of genes involved in stratification, leading to the formation of the skin barrier.

Ethical differentiation and market behavior: An experimental approach

Does ethical differentiation of products affect market behavior? We examined this issue in triopolistic experimental markets where producers set prices. One producer s costs were higher than the others. In two treatments, the additional costs were attributed tocompliance with ethical guidelines. In the third, no justification was provided. Manyparticipants playing the role of consumers reduced their experimental gains by purchasing the ethically differentiated product at a higher price whether or not they knew the amount of extra cost. Individual differences were important (students of business/economics paid smaller premia than others). Finally, we speculate about the observed demand function for ethics and emphasize the use of experimental methodology to complement empirical studies designed to assess the potential market for ethically differentiated products.

Genetic Differentiation of the Cabo Verde Archipelago Population Analysed by STR Polymorphisms

Allele frequencies for 17 STR loci were analyzed in a sample of unrelated males from the Cabo Verde Archipelago. The samples were gathered in such a way that the origin of the subjects was perfectly identified, and they could be included in one of the leeward or windward groups of islands. This study reveals that there are significant differences between both groups of islands, and between Cabo Verdeans and other populations from sub-Sahara Africa including the Guineans, the most probable source population for Cabo Verdeans. This study confirms mtDNA data and, together with HLA and Y chromosome data already published, shows that the Cabo Verde population is substructured and atypical, diverging substantially from mainland sub-Saharan populations. Overall these differences are most probably due to admixture between sub-Saharan slaves brought into the islands and other settlers of European origin. In the absence of a clear indication of a different ethnic composition of the first sub-Saharan settlers of Cabo Verde, the differentiation exhibited in both groups of islands can be most probably be attributed to genetic drift.

Avaliacao dos resultados cirurgicos com a tecnica da resseccao do musculo de Muller-conjuntiva no tratamento da blefaroptose. [Evaluation of the surgery results of Muller's muscle-conjunctival resection in the treatment of blepharoptosis]

OBJECTIVE: To evaluate the results of Muller's muscle-conjunctival resection for correction of blepharoptosis and to discuss the advantages of this procedure. METHODS: 38 patients (39 eyelids) were submitted to Muller's muscle-conjunctival resection. Blepharoptosis varied from 1.0 mm to 3.0 mm (mean: 2.0 mm). The amount of eyelid elevation produced by phenylephrine guided the amount of tissue to be resected. RESULT: 33 eyelids (85%) treated with this procedure were cosmetically acceptable. CONCLUSIONS: Muller's muscle-conjunctival resection procedure is a relatively simple technique for blepharoptosis, with good levator function and positive 10% phenylephrine test. The advantages are: preservation of tarsus and predictable results.

Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injury.

Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine alpha-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission.

Fluoreszenzdiagnostik bei Patienten mit nicht muskelinvasivem Harnblasenkarzinom: Ergebnisse einer Metaanalyse [Fluorescence diagnosis in patients with non-muscle invasive bladder cancer: results of a metaanalysis]

Purpose: Heterogeneous results of single studies with photodynamic diagnosis (PDD) in bladder cancer have been reported. A metaanalysis of prospective studies has now been performed. Material and Methods: The effect of PDD in addition to WLC on a) the diagnosis and b) the therapeutic outcome of primary or recurrent non-muscle invasive bladder cancer (NMIBC) investigated by cystoscopy or transurethral resection was analysed. An electronic database search was performed. Trials were included if they prospectively compared WLC with PDD in bladder cancer. Primary endpoints were additional detection rate, residual tumour at second resection and recurrence-free survival. Results: Significantly more tumour-positive patients were detected with PDD in all patients with non-muscle invasive tumours (= 20%) [95% confidence interval (CI): 8 to 35%] and in CIS patients (= 39%) (CI: 23 to 57%). Residual tumour was significantly less often found after PDD (odds ratio 0.28, CI: 0.15 to 0.52, p<0.0001). Recurrence-free survival was significantly higher at 12 and 24months in the PDD groups than in WLC only groups. Conclusions: More bladder tumour-positive patients are detected by PDD. Best results were found in CIS patients. Diagnosis with PDD results in a more complete resection and a longer recurrence-free survival.

A link between FXYD3 (Mat-8)-mediated Na,K-ATPase regulation and differentiation of Caco-2 intestinal epithelial cells.

FXYD3 (Mat-8) proteins are regulators of Na,K-ATPase. In normal tissue, FXYD3 is mainly expressed in stomach and colon, but it is also overexpressed in cancer cells, suggesting a role in tumorogenesis. We show that FXYD3 silencing has no effect on cell proliferation but promotes cell apoptosis and prevents cell differentiation of human colon adenocarcinoma cells (Caco-2), which is reflected by a reduction in alkaline phosphatase and villin expression, a change in several other differentiation markers, and a decrease in transepithelial resistance. Inhibition of cell differentiation in FXYD3-deficient cells is accompanied by an increase in the apparent Na+ and K+ affinities of Na,K-ATPase, reflecting the absence of Na,K-pump regulation by FXYD3. In addition, we observe a decrease in the maximal Na,K-ATPase activity due to a decrease in its turnover number, which correlates with a change in Na,K-ATPase isozyme expression that is characteristic of cancer cells. Overall, our results suggest an important role of FXYD3 in cell differentiation of Caco-2 cells. One possibility is that FXYD3 silencing prevents proper regulation of Na,K-ATPase, which leads to perturbation of cellular Na+ and K+ homeostasis and changes in the expression of Na,K-ATPase isozymes, whose functional properties are incompatible with Caco-2 cell differentiation.

Hexyl Aminolevulinate-Guided Fluorescence Cystoscopy in the Diagnosis and Follow-up of Patients with Non-Muscle-invasive Bladder Cancer: A Critical Review of the Current Literature.

CONTEXT: Controversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment. EVIDENCE ACQUISITION: We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis. EVIDENCE SYNTHESIS: Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL. CONCLUSIONS: Moderately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required.

Regulation of proliferation and differentiation of human fetal bone cells.

During the last decade, extensive research has been performed in the field of orthopedic medicine to develop cell-based therapies for the restoration of injured bone tissue. We previously demonstrated that human primary fetal bone cells (HFBCs) associated with porous scaffolds induced a bone formation in critical calvaria defect; however, the environmental factors regulating their behavior in culture have not been identified. HFBCs (human fetal femur,12 week development) were compared to marrow-derived human mesenchymal stem cells (HMSCs) for their capacity to proliferate and differentiate into osteoblasts under various culture conditions. When cultured in standard alphaMEM medium, PDGF and FGF-2 increased cell proliferation of both cell types. Investigation of the differentiating capacity of HFBCs and HMSCs in a normal culture medium indicated that HFBCs expressed higher expression levels of RUNX2, OSX, and osteogenic markers compared with HMSCs, while SOX9 was expressed at very low levels in both cells types. However, HMSCs, but not HFBCs enhanced osteoblastic markers in response to osteogenic factors. Surprisingly, BMP-2 with osteogenic factors increased cell numbers and reduced osteoblastic differentiation in HFBCs with the opposite effect seen in HMSCs. Associated with a higher expression of osteoblastic markers, HFBCs produced a higher calcified extra cellular matrix compared with HMSCs. Taken together, data presented in this study suggest that HFBCs have characteristics of osteoprecursor cells that are more advanced in their osteogenesis development compared with mesenchymal stem cells, making fetal cells an interesting biological tool for treatment of skeletal defects and diseases.

Maintenance of neuronal expression of calbindin by a muscular extract in cultures of chick dorsal root ganglion cells.

Calbindin D-28K is a calcium-binding protein which is expressed by subpopulations of dorsal root ganglion cells cultured from 10-day-old (E10) chick embryos. After 7 or 10 days of culture, more than 20% of the ganglion cells are immunostained by an anticalbindin-antiserum; however, after 14 days of culture, the proportion drops to 10%. This fall can be prevented by addition of muscle extract to cultures at 10 days. Thus the transitory expression of calbindin-immunoreactivity by responsive sensory neurons would be not only induced but also maintained by a differentiation factor of muscular origin.

Isolated cerebral metastasis of a triceps muscle leiomyosarcoma: A case report.

Abstract Leiomyosarcomas are rare malignant neoplasms. Intracranial metastases of this tumour are even less frequently observed and have mostly been described from uterine leiomyosarcomas. In this article, we describe the case of a single right frontal subcortical cerebral metastasis in a patient with a right triceps muscle leiomyosarcoma. A right-sided frontal craniotomy with macroscopically complete tumour removal was performed, followed by combined radio-chemotherapy. The patient died 10 months after the initial diagnosis of the intracranial metastasis due to systemic tumour progression, without any evidence of intracranial recurrence.

Between Equity and Differentiation: An Analytical Schema of the Social Function of Education

The educational sphere has an internal function relatively agreed by social scientists. Nonetheless, the contribution that educational systems provide to the society (i.e., their social function) does not have the same degree of consensus. Taking into consideration such theoretical precedent, the current article raises an analytical schema to grasp the social function of education considering a sociological perspective. Starting from the assumption that there is an intrinsic relationship between the internal and social functions of social systems, we suggest there are particular stratification determinants modifying the internal pedagogical function of education, which impact on its social function by creating simultaneous conditions of equity and differentiation. Throughout the paper this social function is considered a paradoxical mechanism. We highlight how this paradoxical dynamic is deployed in different structural levels of the educational sphere. Additionally, we discuss eventual consequences of this paradoxical social function for the inclusion possibilities that educational systems offer to individuals.