Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR?=?0.81; 95% CI: 0.72-0.92; p?=?0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR?=?1.19; 95% CI: 0.63-2.24; ptrend ?=?0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

Clivagem e caracterização de frutalina recombinante produzida em Escherichia coli

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Alimentação e miopia

Dissertação de mestrado em Optometria Avançada

Libertação fotocontrolada de moléculas bioativas a partir de conjugados de cumarinas

Dissertação de mestrado em Química Medicinal

Investor sentiment and the cross-section of stock returns in the French stock market

Dissertação de mestrado em Finanças

Colaboração em inovação: parceiros ou concorrentes?

Dissertação de mestrado em Economia Industrial e da Empresa

Utilização de modelos de simulação para a melhoria de um sistema de restauração: estudo de caso de uma cantina universitária

Dissertação de mestrado em Engenharia Industrial

Cosméticos no Youtube: marcas vs youtubers: em estudo exploratório

Dissertação de mestrado em Design de Comunicação de Moda

Modelação, simulação e implementação de agitação acústica para aplicações em microfluídica

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

Synthesis of iminosugars through diastereo/enantioselective diels-alder cycloaddition

Tese de Doutoramento em Ciências (Especialidade em Química)

Multithreading RTOS processor design

Tese de Doutoramento Plano Doutoral em Engenharia Eletrónica e de Computadores.

Novas funcionalidades para dispositivos médicos invasivos com imagem

Tese de Doutoramento em Engenharia Eletrónica e de Computadores.

Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Three-dimensional technology facilitates surgical performance of novice laparoscopy surgeons: a quantitative assessment on a porcine kidney model

Objective To determine whether the use of 3-dimensional (3D) imaging translates into a better surgical performance of naïve urologic laparoscopic surgeons during pyeloplasty (PY) and partial nephrectomy (PN) procedures. Materials and Methods Eighteen surgeons without any previous laparoscopic experience were randomly assigned to perform PY and PN in a porcine model using initially 2-dimensional (2D) and 3D laparoscopy. A surgical performance score was rated by an "expert" tutor through a modified 5-item global rating scale contemplating operative field view, bimanual dexterity, efficiency, tissue handling, and autonomy. Overall surgical time, complications, subjective perception of participating surgeons, and inconveniences related to the 3D vision were recorded. Results No difference in terms if operative time was found between 2D or 3D laparoscopy for both the PY (P =.51) and the PN (P =.28) procedures. A better rate in terms of surgical performance score was noted by the tutors when the study participants were using 3D vs 2D, for both PY (3.6 [0.8] vs 3.0 [0.4]; P =.034) and PN (3.6 [0.51] vs 3.15 [0.63]; P =.001). No complications occurred in any of the procedures. Most (77.2%) of the participating na??ve laparoscopic surgeons had the perception that 3D laparoscopy was overall easier than 2D. Headache (18.1%), nausea (18.1%), and visual disturbance (18.1%) were the most common issues reported by the surgeons during 3D procedures. Conclusion Despite the absence of translation in a shorter operative time, the use of 3D technology seems to facilitate the surgical performance of naive surgeons during laparoscopic kidney procedures on a porcine model.

Morphofunctional study of the junction between the left atrium and the pulmonary veins in patient with pulmonary hypertension

OBJECTIVE: To study the arrangement of the myocardial fiber bundles at the pulmonary venous left atrial junction in patients with pulmonary hypertension, and to discuss the pathophysiological importance of this element in the etiology of acute pulmonary edema. METHODS: We obtained 12 hearts and their pulmonary vein extremities from postmortem examinations of patients with the anatomicopathological diagnosis of acute pulmonary edema. The specimens, which had no grossly visible morphological cardiac alterations, were fixed in 10% formalin, and the muscular arrangement of the pulmonary venous left atrial junctions was analyzed. This material was then isolated, embedded in paraffin, underwent serial cutting (50 µm of thickness), and was stained with Azam's trichrome. RESULTS: We observed in our specimens that: a) the myocardial fiber bundles that originate in the atrial wall and involve the openings of the pulmonary veins were fewer than those observed in healthy material; b) the myocardial fiber bundles that extend into the pulmonary veins were shorter than those found in material originating from individuals with no pulmonary hypertension. CONCLUSION: Anatomical changes that result in a reduction in the amount of myocardial fiber bundles in the pulmonary venous left atrial junction, isolated or associated with other factors, may be the cause of disorders in pulmonary circulation, leading to an increase in pulmonary venous pressure, and, consequently, to acute pulmonary edema.