Role of Age and Sex in the Diagnosis of Early-stage Malignant Melanoma: A Cross-Sectional study.

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). This aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2430 patients with MM were recruited. Cases of in situ-T1 MM were more frequent than T2-T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r   = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0-29 years (1.18), and 30-59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis-T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM.

Large gangliocytic paraganglioma of the duodenum: A rare entity.

Gangliocytic paragangliomas are rare tumors that almost exclusively occur within the second portion of the duodenum. Although these tumors generally have a benign clinical course, they have the potential to recur or metastasize to regional lymph nodes. The case report presented here describes a 57-year-old female patient with melena, progressive asthenia, anemia, and a mass in the second-third portion of the duodenum that was treated by local excision. The patient was diagnosed with a friable bleeding tumor. The histologic analysis showed that the tumor was a 4 cm gangliocytic paraganglioma without a malignant cell pattern. In the absence of local invasion or distant metastasis, endoscopic resection represents a feasible, curative therapy. Although endoscopic polypectomy is currently considered the treatment of choice, it is not recommended if the size of the tumor is > 3 cm and/or there is active or recent bleeding. Patients diagnosed with a gangliocytic paraganglioma should be closely followed-up for possible local recurrence.

Role of double-balloon enteroscopy in malignant small bowel tumors.

AIMTo assess the double-balloon enteroscopy (DBE) role in malignant small bowel tumors (MSBT). METHODS This is a retrospective descriptive study performed in a single center. All consecutive patients who underwent a DBE with final diagnosis of a malignant neoplasm from 2004 to 2014 in our referral center were included. Patient demographic and clinical pathological characteristics were recorded and reviewed. MSBT diagnosis was achieved either by DBE directed biopsy with multiple tissue sampling, endoscopic findings or histological analysis of surgical specimen. We have analyzed double-balloon enteroscopy impact in outcome and clinical course of these patients. RESULTS Of 627 patients, 28 (4.5%) (mean age = 60 ± 17.3 years) underwent 30 procedures (25 anterograde, 5 retrograde) and were diagnosed of a malignant tumor. Patients presented with obscure gastrointestinal bleeding (n = 19, 67.9%), occlusion syndrome (n = 7, 25%) and diarrhea (n = 1, 3.6%). They were diagnosed by DBE biopsy (n = 18, 64.3%), histological analysis of surgical specimen (n = 7, 25%) and unequivocal endoscopic findings (n = 2, 7.1%). Gastrointestinal stromal tumor (n = 8, 28.6%), adenocarcinoma (n = 7, 25%), lymphoma (n = 4, 14.3%), neuroendocrine tumor (n = 4, 14.3%), metastatic (n = 3, 10.7%) and Kaposi sarcoma (n = 1, 3.6%) were identified. DBE modified outcome in 7 cases (25%), delaying or avoiding emergency surgery (n = 3), modifying surgery approach (n = 2) and indicating emergency SB partial resection instead of elective approach (n = 2). CONCLUSION DBE may be critical in the management of MSBT providing additional information that may be decisive in the clinical course of these patients.

Adjuvant treatment of melanoma.

Melanomas represent 4% of all malignant tumors of the skin, yet account for 80% of deaths from skin cancer.While in the early stages patients can be successfully treated with surgical resection, metastatic melanoma prognosis is dismal. Several oncogenes have been identified in melanoma as BRAF, NRAS, c-Kit, and GNA11 GNAQ, each capable of activating MAPK pathway that increases cell proliferation and promotes angiogenesis, although NRAS and c-Kit also activate PI3 kinase pathway, including being more commonly BRAF activated oncogene. The treatment of choice for localised primary cutaneous melanoma is surgery plus lymphadenectomy if regional lymph nodes are involved. The justification for treatment in addition to surgery is based on the poor prognosis for high risk melanomas with a relapse index of 50-80%. Patients included in the high risk group should be assessed for adjuvant treatment with high doses of Interferon- α 2b, as it is the only treatment shown to significantly improve disease free and possibly global survival. In the future we will have to analyze all these therapeutic possibilities on specific targets, probably associated with chemotherapy and/or interferon in the adjuvant treatment, if we want to change the natural history of melanomas.

Light-regulated plant growth and development.

Plants are sessile and photo-autotrophic; their entire life cycle is thus strongly influenced by the ever-changing light environment. In order to sense and respond to those fluctuating conditions higher plants possess several families of photoreceptors that can monitor light from UV-B to the near infrared (far-red). The molecular nature of UV-B sensors remains unknown, red (R) and far-red (FR) light is sensed by the phytochromes (phyA-phyE in Arabidopsis) while three classes of UV-A/blue photoreceptors have been identified: cryptochromes, phototropins, and members of the Zeitlupe family (cry1, cry2, phot1, phot2, ZTL, FKF1, and LKP2 in Arabidopsis). Functional specialization within photoreceptor families gave rise to members optimized for a wide range of light intensities. Genetic and photobiological studies performed in Arabidopsis have shown that these light sensors mediate numerous adaptive responses (e.g., phototropism and shade avoidance) and developmental transitions (e.g., germination and flowering). Some physiological responses are specifically triggered by a single photoreceptor but in many cases multiple light sensors ensure a coordinated response. Recent studies also provide examples of crosstalk between the responses of Arabidopsis to different external factors, in particular among light, temperature, and pathogens. Although the different photoreceptors are unrelated in structure, in many cases they trigger similar signaling mechanisms including light-regulated protein-protein interactions or light-regulated stability of several transcription factors. The breath and complexity of this topic forced us to concentrate on specific aspects of photomorphogenesis and we point the readers to recent reviews for some aspects of light-mediated signaling (e.g., transition to flowering).

Application of the european customer satisfaction index to postal services. Structural equation models versus partial least squars

Customer satisfaction and retention are key issues for organizations in today’s competitive market place. As such, much research and revenue has been invested in developing accurate ways of assessing consumer satisfaction at both the macro (national) and micro (organizational) level, facilitating comparisons in performance both within and between industries. Since the instigation of the national customer satisfaction indices (CSI), partial least squares (PLS) has been used to estimate the CSI models in preference to structural equation models (SEM) because they do not rely on strict assumptions about the data. However, this choice was based upon some misconceptions about the use of SEM’s and does not take into consideration more recent advances in SEM, including estimation methods that are robust to non-normality and missing data. In this paper, both SEM and PLS approaches were compared by evaluating perceptions of the Isle of Man Post Office Products and Customer service using a CSI format. The new robust SEM procedures were found to be advantageous over PLS. Product quality was found to be the only driver of customer satisfaction, while image and satisfaction were the only predictors of loyalty, thus arguing for the specificity of postal services

Networks of PhD Students and Academic Performance: A Comparison across Countries

In this article we compare regression models obtained to predict PhD students’ academic performance in the universities of Girona (Spain) and Slovenia. Explanatory variables are characteristics of PhD student’s research group understood as an egocentered social network, background and attitudinal characteristics of the PhD students and some characteristics of the supervisors. Academic performance was measured by the weighted number of publications. Two web questionnaires were designed, one for PhD students and one for their supervisors and other research group members. Most of the variables were easily comparable across universities due to the careful translation procedure and pre-tests. When direct comparison was notpossible we created comparable indicators. We used a regression model in which the country was introduced as a dummy coded variable including all possible interaction effects. The optimal transformations of the main and interaction variables are discussed. Some differences between Slovenian and Girona universities emerge. Some variables like supervisor’s performance and motivation for autonomy prior to starting the PhD have the same positive effect on the PhD student’s performance in both countries. On the other hand, variables like too close supervision by the supervisor and having children have a negative influence in both countries. However, we find differences between countries when we observe the motivation for research prior to starting the PhD which increases performance in Slovenia but not in Girona. As regards network variables, frequency of supervisor advice increases performance in Slovenia and decreases it in Girona. The negative effect in Girona could be explained by the fact that additional contacts of the PhD student with his/her supervisor might indicate a higher workload in addition to or instead of a better advice about the dissertation. The number of external student’s advice relationships and social support mean contact intensity are not significant in Girona, but they have a negative effect in Slovenia. We might explain the negative effect of external advice relationships in Slovenia by saying that a lot of external advice may actually result from a lack of the more relevant internal advice

Social capital and the equilibrium number of entrepreneurs

Social capital is viewed either as a proprietary asset that serves private interests, including those of entrepreneurs, or as a collective asset that supports trust-based transactions saving on transaction costs both in markets and within the boundaries of firms, and benefiting society as a whole. This paper explains the relative specialization between entrepreneurs and market-governed exchanges as a result of the interaction between social capital that lowers transaction costs, and the scale economies of ability in managerial jobs (Lucas 1978). The main hypothesis formulated in the paper is that higher social capital will benefit the hierarchy relatively more than the market as a governance mechanism, and therefore in economies with higher social capital, the equilibrium number of entrepreneurs will be lower and their average span of control larger than in economies with lower social capital. The empirical evidence, with data from the Spanish Autonomous Communities, is consistent with this prediction.

A-kinase anchoring proteins: scaffolding proteins in the heart.

The pleiotropic cyclic nucleotide cAMP is the primary second messenger responsible for autonomic regulation of cardiac inotropy, chronotropy, and lusitropy. Under conditions of prolonged catecholaminergic stimulation, cAMP also contributes to the induction of both cardiac myocyte hypertrophy and apoptosis. The formation of localized, multiprotein complexes that contain different combinations of cAMP effectors and regulatory enzymes provides the architectural infrastructure for the specialization of the cAMP signaling network. Scaffolds that bind protein kinase A are called &quot;A-kinase anchoring proteins&quot; (AKAPs). In this review, we discuss recent advances in our understanding of how PKA is compartmentalized within the cardiac myocyte by AKAPs and how AKAP complexes modulate cardiac function in both health and disease.

Critical role for the lactate transporter, monocarboxylate transporter 1 (mct1), in the regeneration of peripheral nerves

Axons, and particularly regenerating axons, have high metabolic needs in order to maintain critical functions such as axon transport and membrane depolarization. Though some of the required energy likely comes form extracellular glucose and ATP generated in the soma, we and others hypothesize that some of the energy may be supplied by lactate. Unlike glucose that requires glycolytic enzymes to produce pyruvate, lactate can be converted directly to pyruvate by lactate dehydrogenase and transported into mitochondria for oxidative metabolism. In order to be transported into or out of cells, lactate requires specific monocarboxylate transporters (MCTs), the most abundant of which is MCT1. If MCT1 and lactate are critical for nerve function and regeneration, we hypothesize that MCT1 heterozygote null mice, which appear phenotypically normal despite having approximately 40% MCT1 as compared to wildtype littermate mice, would have reduced capacity for repair following nerve injury. To investigate this, adult MCT1 heterozygote null mice or wild-type mice underwent unilateral sciatic nerve crush in the proximal thigh. We found that regeneration of the sciatic nerve, as measured by recovery of compound muscle action potentials (CMAP) in the lateral plantar muscles following proximal sciatic nerve stimulation, was delayed from a median of 21 days in wildtype mice to 38.5 days in MCT1 heterozygote mice. In fact, half of the MCT1 heterozygote null mice had no recovery of CMAP by the endpoint of the study at 42 days, while all of the wild-type mice had recovered. In addition, the maximal amplitude of CMAP recovery in MCT1 heterozygote mull mice was reduced from a mean of 3 mV to 0.5 mV. As would be expected, the denervated gastrocnemius muscle of MCT1 heterozygote null mice remained atrophic at 42 days compared to wild-type mice. Our experiments show that lactate supplied through MCT1 is necessary for nerve regeneration. Experiments are underway to determine whether loss of MCT1 prevents nerve regrowth directly due to reduced energy supply to axons or indirectly by dysfunctional Schwann cells normally dependent on lactate supply through MCT1.

Morphological and physiological species-dependent characteristics of the rodent Grueneberg ganglion.

In the mouse, the Grueneberg ganglion (GG) is an olfactory subsystem implicated both in chemo- and thermo-sensing. It is specifically involved in the recognition of volatile danger cues such as alarm pheromones and structurally-related predator scents. No evidence for these GG sensory functions has been reported yet in other rodent species. In this study, we used a combination of histological and physiological techniques to verify the presence of a GG and investigate its function in the rat, hamster, and gerbil comparing with the mouse. By scanning electron microscopy (SEM) and transmitted electron microscopy (TEM), we found isolated or groups of large GG cells of different shapes that in spite of their gross anatomical similarities, display important structural differences between species. We performed a comparative and morphological study focusing on the conserved olfactory features of these cells. We found fine ciliary processes, mostly wrapped in ensheating glial cells, in variable number of clusters deeply invaginated in the neuronal soma. Interestingly, the glial wrapping, the amount of microtubules and their distribution in the ciliary processes were different between rodents. Using immunohistochemistry, we were able to detect the expression of known GG proteins, such as the membrane guanylyl cyclase G and the cyclic nucleotide-gated channel A3. Both the expression and the subcellular localization of these signaling proteins were found to be species-dependent. Calcium imaging experiments on acute tissue slice preparations from rodent GG demonstrated that the chemo- and thermo-evoked neuronal responses were different between species. Thus, GG neurons from mice and rats displayed both chemo- and thermo-sensing, while hamsters and gerbils showed profound differences in their sensitivities. We suggest that the integrative comparison between the structural morphologies, the sensory properties, and the ethological contexts supports species-dependent GG features prompted by the environmental pressure.

L'analyse des renvois régionaux et interrégionaux en pratique médicale ambulatoire. [Analysis of regional and interregional referrals in ambulatory medical practice].

This article examines, in two Swiss cantons, the interdependence from a medical care point of view of various regions (health planning zones in one canton, political districts in the other). The volume and the destination of patient referrals prescribed by physicians in ambulatory practice are analyzed. The available data (on 1609 referrals) were gathered by the practitioners themselves, during a National Ambulatory Medical Care Survey type study in February-March 1981, in which 203 physicians participated. Several indicators are proposed (including an integration coefficient and an attraction coefficient for each zone); they show marked differences among the regions. This dynamic approach, based on the effective behavior of physicians, appears to be of major interest for health planning purposes (as compared with the frequent practice to use mainly parameters in relation with the availability of care services--the "supply"--numbers of professionals and/or health facilities).

Iniciació a la dinamització del futbol sala als centres penitenciaris

El futbol sala és, sense cap mena de dubte, l’esport d’equip més practicat a tots els centres penitenciaris del nostre territori. I és així, bàsicament, perquè és l’activitat més demanada pels nostres col·lectius d’interns que, a cada centre, troben en aquest esport la millor manera de transmetre les seves habilitats esportives i físiques. És, en definitiva, el “germà petit” de l’esport rei –el futbol– i, per tant, qui més qui menys el sap i el vol practicar. Malgrat que parlem d’un esport relativament conegut per la comunitat de tècnics esportius, no farà cap nosa intentar cercar quins són els aspectes bàsics que s’haurien de tenir en compte a l’hora de dinamitzar una activitat esportiva d’aquesta disciplina. És per aquest motiu que aquest document s’adreça a tots els tècnics esportius que volen dinamitzar una activitat que per a ells potser és desconeguda. No es tracta, doncs, d’aprofundir-hi molt, ans al contrari, es tracta d’una aproximació al món del futbol sala des d’un vessant educatiu. L’objectiu del curs és aconseguir que tots els tècnics esportius obtinguin eines i coneixements per saber planificar, dissenyar, controlar i avaluar els diferents recursos que tenen al seu centre a fi que puguin iniciar qualsevol intern en la pràctica del futbol sala.

Spatio-temporal micromeasurements of the oxygen uptake in the developing chick embryo.

A method has been developed for the determination of the oxygen uptake of small areas (0.01 mm2) in an entire chick embryo cultured in vitro under defined metabolic conditions. It is based on the recordings of the spectral changes of the hemoglobin used as oxygen source for the respiring tissue (Barzu and Borza, 1967). Rapid scanning of the hemoglobin absorbance over the preparation allows a comparison of the O2 uptake of various regions. Values of the order of 10(-2) 1 O2 . min-2 are measured in less than 10 sec with a spatial resolution of 100 micron. The differentiation of embryonic tissue is not disturbed by the measurements. The O2 diffusion in the media and in the tissue has been analyzed by digital simulation. The O2 uptake of the Hensen's node was measured from embryos starting at the stage of definitive primitive streak (stage 4) up to the stage of 10 somites. It increases from 0.6 to 1.1 nl . h-1 with a marked acceleration between stages 4 and 5. The values corrected for the protein content of the Hensen's node at stage 4, 5, 6 and 8 are 32, 30 and 28 microliter . mg-1 . h-1 respectively. The first scanning results show different patterns of the O2 utake at the level of the Hensen's node and of the neural plate. At stage 6-7, the corrected O2 uptake is 30 microliter . mg-1 . h-1 for . the former and 43 microliter . mg-1 . h-1 for the latter.

Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cells from melanoma patients reveals inefficient antigen processing.

Telomerase is a ribonucleoprotein complex responsible for the maintenance of the length of the telomeres during cell division, which is active in germ-line cells as well as in the vast majority of tumors but not in most normal tissues. The wide expression of the human telomerase catalytic subunit (hTERT) in tumors makes it an interesting candidate vaccine for cancer. hTERT-derived peptide 540-548 (hTERT(540)) has been recently shown to be recognized in an HLA-A*0201-restricted fashion by T cell lines derived from peptide-stimulated peripheral blood mononuclear cells (PBMC) from healthy donors. As a first step to the inclusion of this peptide in immunotherapy clinical trials, it is crucial to assess hTERT(540)-specific T cell reactivity in cancer patients as well as the ability of hTERT-specific CD8(+) T lymphocytes to recognize and lyse hTERT-expressing target cells. Here, we have analyzed the CD8(+) T cell response to peptide hTERT(540) in HLA-A*0201 melanoma patients by using fluorescent HLA-A*0201/hTERT(540) peptide tetramers. HLA-A*0201/hTERT(540) tetramer(+) CD8(+) T cells were readily detected in peptide-stimulated PBMC from a significant proportion of patients and could be isolated by tetramer-guided cell sorting. hTERT(540)-specific CD8(+) T cells were able to specifically recognize HLA-A*0201 cells either pulsed with peptide or transiently transfected with a minigene encoding the minimal epitope. In contrast, they failed to recognize hTERT-expressing HLA-A*0201(+) target cells. Furthermore, in vitro proteasome digestion studies revealed inadequate hTERT processing. Altogether, these results raise questions on the use of hTERT(540) peptide for cancer immunotherapy.