The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA.

Centromeres are the chromosomal domains required to ensure faithful transmission of the genome during cell division. They have a central role in preventing aneuploidy, by orchestrating the assembly of several components required for chromosome separation. However, centromeres also adopt a complex structure that makes them susceptible to being sites of chromosome rearrangements. Therefore, preservation of centromere integrity is a difficult, but important task for the cell. In this review, we discuss how centromeres could potentially be a source of genome instability and how centromere aberrations and rearrangements are linked with human diseases such as cancer.

[The opinion of psychiatry residents about social interaction during the feedback in medical education]. / Importancia de la interacción social en la retroalimentación, según residentes de Psiquiatría.

UNLABELLED: In Medical Education, feedback is an instrument that informs the trainees about their learning process and how to make the necessary changes. Feedback enables learners to monitor their progress and provides direction for improvement. Effective feedback is useful to improve the performance, clinical skills, communication skills, and treatment of patients. It is essential when teaching clinical interview skills to psychiatry residents. Feedback necessarily involves social interaction between teachers and trainees. AIM: To analyze the perception of psychiatry residents about social interaction during the feedback received during their training. MATERIAL AND METHODS: Qualitative study, using the Grounded theory method. Nine interviews were performed to adult psychiatry residents of the University of Concepción and one to a recently graduated psychiatrist. Data were analyzed using open coding. RESULTS: We found four emerging categories: Socialization, roles and hierarchy, invitation to integration and teacher involvement. CONCLUSIONS: The effectiveness of feedback lies in the establishment of a minimal teacher-resident social relationship, in which feedback occurs naturally.

Importancia de la interacción social en la retroalimentación, según residentes de Psiquiatría / The opinion of psychiatry residents about social interaction during the feedback in medical education

In Medical Education, feedback is an instrument that informs the trainees about their learning process and how to make the necessary changes. Feedback enables learners to monitor their progress and provides direction for improvement. Effective feedback is useful to improve the performance, clinical skills, communication skills, and treatment of patients. It is essential when teaching clinical interview skills to psychiatry residents. Feedback necessarily involves social interaction between teachers and trainees. Aim: To analyze the perception of psychiatry residents about social interaction during the feedback received during their training. Material and Methods: Qualitative study, using the Grounded theory method. Nine interviews were performed to adult psychiatry residents of the University of Concepción and one to a recently graduated psychiatrist. Data were analyzed using open coding. Results: We found four emerging categories: Socialization, roles and hierarchy, invitation to integration and teacher involvement. Conclusions: The effectiveness of feedback lies in the establishment of a minimal teacher-resident social relationship, in which feedback occurs naturally.

An incidental finding of breast cancer after breast injury.

We report of a 52-year-old woman presenting with a breast palpable mass after a trauma due to accidental fall. The patient came to our attention to perform an ultrasonographic examination because of the persistence of the mass after the trauma. The exam showed an hypo-anechoic oval formation with blurred margins and no vascularization at Power Doppler, located to the union of the upper quadrants of the right breast. The patient also performed mammographic examination, which showed an unknown oval radiopaque area. The findings were consistent with post-traumatic hematoma, even in relation to the anamnestic data, therefore we recommended anti-inflammatory therapy and a new check in fifteen days. The next ultrasonographic examination showed the persistence of the mass, slightly reduced in size, so we tried to achieve a more detailed diagnosis by performing MRI; however, the diagnostic doubt still remained, so we decided to perform a US-guided core-biopsy: the histological diagnosis was infiltrating ductal carcinoma of the breast. A review of the literature confirmed that breast lesions often are incidental findings after a breast trauma.

Short- and long-term overall results of liver retransplantation: "Doce de Octubre" hospital experience.

INTRODUCTION: The liver retransplantation rate in Spain is about 6%. The main causes are primary nonfunction, vascular complications, chronic rejection, and recurrent liver disease. The results of this procedure are worse than those of first transplantations. PATIENTS AND METHODS: This retrospective study evaluated our experience with 54 retransplantations performed between January 1992 and December 2006, which were 5.6% of the 960 orthotopic liver transplantations (OLT) during this period. RESULTS: In this study, 34.7% of the retransplantations were performed between 4 and 30 days after the first transplantation; another 34.7% were within 1 year. Also, 48.9% of the retransplantations were performed in urgent situations. The main causes for retransplantation during the first month were primary hepatic failure (n = 14) and vascular complications (n = 4). After the first month the main causes were chronic rejection (n = 9), recurrence of hepatic disease (n = 3), and biliary complications (n = 4). Postoperative mortality was 23.9% and morbidity was 76.3%. However, 21.2% of the patients needed a third transplant. The overall rate of patient survival was 60.4% (n = 32) and of graft survival was 56.6% (n = 30). The 5-year actuarial graft survival rate was 65.4% with a mean survival time of 89.84 +/- 8.72 months; the 5-year patient survival rate was 64% with a mean survival time of 114.7 +/- 12.53 months. Worse survival was observed in chronic rejection and in retransplantations performed between 31 and 360 days. CONCLUSIONS: Liver retransplantation presents greater surgical complexity than the first transplantation, but is a good option for patients with failure of the first graft with a 5-year patient and graft survival rate greater than 65%.

Oxidized low density lipoproteins induce apoptosis in human lymphocytes: involvement of mitogen-activated protein kinases.

Oxidized low density lipoproteins (oxLDL), macrophages and T-lymphocytes are present in atherosclerotic lesions. We and others have shown that oxLDL is cytotoxic for macrophages, endothelial, smooth muscle and activated T-lymphocytes and induce apoptosis. Here we demonstrate that (i) oxidized LDL (oxLDL), oxidized VLDL (oxVLDL) and hydrogen peroxide (H2O2) induce apoptosis in human T-lymphocytes and (ii) mitogen-activated protein kinases are involved in this process. Apoptosis was monitored by immunofluorescence microscopy and flow cytometry for annexin V binding, Apo 2.7 expression, the TUNEL reaction and caspase 3 activity. In the presence of oxLDL (100 microg/ml), oxVLDL (50 microg/ml) and H2O2 (5 mM), the fraction of apoptotic cells increased within 6 hours to more than 70%. Preincubation of lymphocytes with the MAPKK inhibitor PD-98059 and the p38MAPK inhibitor SB-203580 almost completely abolished these effects. Furthermore, oxLDL and H2O2 but not native LDL strongly enhanced phosphorylation of JNK, p38MAPK and p42/44MAPK. The results suggest that in the resting lymphocyte apoptosis triggered by oxidized lipoproteins and oxidative stress depends on the activation of p44/42MAPK and p38MAPK cascades.

Synthesis of a functional information with anatomical landmarks by multiresolution fusion of brain images.

In order to help clinicians with the diagnosis of neurodegenerative diseases, we provide a synthetic functional information located in relation with anatomical structures. The final image is processed by multimodal data fusion between SPECT and MR images. We propose a new method for the management of such multiresolution data, in which a geometrical model allows an accurate correspondence of voxels from both images, while preserving at best both original pieces of information. We use this matching method to replace the interpolation step in the compulsory image registration of the data fusion process. The geometrical model is first built from registration parameters. Computational geometry algorithms, applied to this model, allow the computation of numerical values used to process the final information. The method has been applied to brain perfusion and neurotransmission SPECT images.

Extraction of epileptogenic foci from PET and SPECT images by fuzzy modeling and data fusion.

During the presurgical evaluation of medically intractable epilepsy, isotopic functional imagery provides an increasing amount of data concerning the potential location of the focus. The aim of this study is to facilitate the surgical decision by presenting an image fusion method able to extract epileptogenic foci from periictal single photon emission computed tomography (SPECT), interictal SPECT, fluoro-desoxy-glucose (FDG) position emission tomography (PET), and flumazenil PET. After spatial coregistration, the images are converted into fuzzy maps whose membership functions indicate the pathological degree of each voxel, according to each modality. These maps are then fused together thanks to a combination operator managing uncertainty (due to the sensitivity) and imprecision (due to poor resolution and partial volume effect) of the images. In the framework of possibilistic theory, this operator mimics the way the physicians evaluate and compare the various exams. The technique was successfully tested on simulated images with well-defined abnormalities, in terms of size and intensity. A preliminary clinical study was also performed and gave results in accordance with the "gold standard" investigation (deep electrodes or postsurgical outcome) in 11 patients out of 12.

Effects of two electrical stimulation frequencies in thigh muscle after knee surgery.

The purpose of this study was to compare the effects of two protocols of electrical stimulation combined with voluntary contractions on the recovery of thigh muscles after anterior cruciate ligament (ACL) surgery. Ten sportsmen with a mean age of 26 yrs were randomly assigned into two groups: a 80 Hz stimulated group (5 patients) and a 20 Hz stimulated group (5 patients). All patients received electrical stimulation of the quadriceps femoris, five days a week, for 12 weeks, and had a standard program of voluntary contractions. Muscle and fat volumes of the thigh were assessed using MRI before surgery and after 12 weeks of rehabilitation. Quadriceps and hamstring muscle strength were evaluated by isokinetic measurements. Twelve weeks after surgery, the quadriceps peak torque deficit in the operated limb with respect to the non operated limb at 180 degrees /s and 240 degrees /s was significantly (p < 0.05) less in the 20 Hz group than in the 80 Hz group. This difference was not confirmed when comparing the pre-surgery quadriceps peak torque of the operated limb with the post-surgery one. Subcutaneous fat volume was increased for the two groups at the post-surgery test. This increase was significantly (p < 0.05) greater for the 80 Hz group. Thigh muscle volume deficit was not significantly different between the two groups.

Glandular kallikreins in the teleost Cyprinus carpio: tissue distribution, possible involvement in prolactin processing, and effect of 17 beta-estradiol in vivo.

We examined glandular kallikrein (GK), a putative prolactin processing protease, in the teleost Cyprinus carpio. When employing an anti-Centropristis striata GK antibody proteins of 39 kDa in muscle, 52 kDa in gill, 52 kDa in kidney, and two proteins of 46 and 72 kDa in pituitary gland were detected. Immunoreactive kallikreins were recognized in intermuscle cell tissue, epithelial gill cells, apical region of tubular cells, and prolactin producing lactotrophs in pituitary gland, suggesting a osmoregulatory role for this enzyme. We found three prolactin (PRL) variants using anti-tilapia PRL antibodies, in pituitary gland 23 and 16 kDa, and in plasma 23 and 22 kDa forms. Clearly co-localization of GK and PRL in lactotrophs could be demonstrated. In winter-acclimatized male carp, where the pituitary PRL level is low, 17beta-estradiol treatment increased PRL but not GK immunoreactivity. In contrast to GK and PRL co-regulation by estrogen in mammalian pituitary gland, no similar effect on immunoreactive PRL and GK was observed in the ichtyc pituitary. No changes in GK immunostaining occurred in gill or muscle tissue in response to estrogen treatment. These results, taken with the observation of significantly increased GK immunoreactivity in the apical region of kidney tubular cells in estrogen treated male carp, indicate that the regulation of GK expression in pituitary and kidney could be different in fish with respect to mammals.

Fusion in medical imaging: theory, interests and industrial applications.

The accumulation of several data coming from medical images and signals, expert knowledge and databases is becoming very common for the study of a given pathology. The aggregation of all this information is mentally performed by a clinician, and generally allows for a better medical decision in clinical studies. We propose in this article a fusion method that models this aggregation process. This method is a three step scheme, that first transforms all the available information in a common theoretical frame, then aggregates these data using their redundancy and their conflicts, and finally computes a new information synthesizing all the initial knowledge. We first introduce in this article the fusion scheme and its theoretical aspects, and we particularly focus on the three steps of the process. We then detail the software implementation of this concept, achieved in collaboration with SEGAMI Corporation Inc. We finally apply this concept to a real clinical problem, the study of Alzheimer's disease using MR and SPECT images, and we show very encouraging preliminary results.

Automatic segmentation of subcortical brain structures in MR images using information fusion.

This paper reports a new automated method for the segmentation of internal cerebral structures using an information fusion technique. The information is provided both by images and expert knowledge, and consists in morphological, topological, and tissue constitution data. All this ambiguous, complementary and redundant information is managed using a three-step fusion scheme based on fuzzy logic. The information is first modeled into a common theoretical frame managing its imprecision and incertitude. The models are then fused and a decision is taken in order to reduce the imprecision and to increase the certainty in the location of the structures. The whole process is illustrated on the segmentation of thalamus, putamen, and head of the caudate nucleus from expert knowledge and magnetic resonance images, in a protocol involving 14 healthy volunteers. The quantitative validation is achieved by comparing computed, manually segmented structures and published data by means of indexes assessing the accuracy of volume estimation and spatial location. Results suggest a consistent volume estimation with respect to the expert quantification and published data, and a high spatial similarity of the segmented and computed structures. This method is generic and applicable to any structure that can be defined by expert knowledge and morphological images.

Peroneus brevis tendon transfer in neglected tears of the Achilles tendon.

BACKGROUND: We present the results of a single-center, single-surgeon study in 59 patients with a fresh (4 women and 23 men; mean age, 43.6 +/- 8.8 years) or a neglected (1 woman and 21 men; mean age, 41.3 +/- 7.4 years) Achilles tendon rupture. METHODS: Patients with a fresh rupture were operated on using end-to-end suture, and patients with a neglected rupture received the tendon of the peroneus brevis as an autologous graft. Patients were assessed during the sixth postoperative week, and during the sixth postoperative month. They were discharged within 1 year after the operation, and were reviewed at an average of 53 +/- 13 months after surgery. RESULTS: Patients were generally satisfied with the procedure, but those with a neglected rupture tended to have a greater postoperative complication rate, greater loss of isokinetic strength variables at high speeds, and greater loss of calf circumference. CONCLUSION: The management of acute and neglected subcutaneous tears of the Achilles tendon by peroneus tendon transfer is safe but technically demanding. It affords good recovery, even in patients with a neglected rupture of 6 weeks' to 9 months' duration. Patients with a neglected rupture are at a slightly greater risk of postoperative complications, and their ankle plantar flexion strength can be reduced.

A general framework for the fusion of anatomical and functional medical images.

The collection of various data coming from anatomical and functional imagery is becoming very common for the study of a given pathology, and their aggregation generally allows for a better medical decision in clinical studies. A fusion process is described in this article for the modeling of this aggregation. The process is illustrated in the case of anatomical and functional images of the brain, but the general principle may be extended to other organs. The whole three-step fusion process based on possibilistic logic is detailed and a new class of fusion operator is introduced. The use of fuzziness in the process in general and in the operator in particular allows for the management of uncertainty and imprecision inherent to the images. The fusion process is illustrated in two clinical cases: the study of Alzheimer's disease by MR/SPECT fusion and the study of epilepsy by MR/SPECT/PET fusion. Results are presented and evaluated, and a preliminary clinical validation is achieved. The assessment of the method is encouraging, allowing its application on several clinical problems.

Tissue segmentation on MR images of the brain by possibilistic clustering on a 3D wavelet representation.

An algorithm for the segmentation of a single sequence of three-dimensional magnetic resonance (MR) images into cerebrospinal fluid, gray matter, and white matter classes is proposed. This new method is a possibilistic clustering algorithm using the fuzzy theory as frame and the wavelet coefficients of the voxels as features to be clustered. Fuzzy logic models the uncertainty and imprecision inherent in MR images of the brain, while the wavelet representation allows for both spatial and textural information. The procedure is fast, unsupervised, and totally independent of any statistical assumptions. The method is tested on a phantom image, then applied to normal and Alzheimer's brains, and finally compared with another classic brain tissue segmentation method, affording a relevant classification of voxels into the different tissue classes.

Benefit of endurance training in elderly people over a short period is reversible.

The present study assessed daily activity, physical capacity and body composition in 11 initially sedentary healthy subjects [5 men and 6 women, mean age 62.8 (SD 2.7) years] before training (T(o)), after completion of 7 (T(7w)) and 14 (T(14w)) weeks of training, and again 6 (T(6m)) and 12 (T(12m)) months after training. The mean daily activity index decreased from T(7w) to T(12m) reaching a lower level than at T(o) [T(12m) - T(o) = -1.5 (SD 4.6) units, P = 0.18]. Mean maximal oxygen uptake (VO(2max)) and its corresponding mean power output (Wdot(max)) were increased by 12.5 (SD 6.6)% (P = 0. 003) and 22.8 (SD 12.8)% (P = 0.003), respectively, at T(14w), and returned to their T(o) levels within 1 year. Mean body mass (m(b)) remained stable until T(6m) but increased significantly by 2.6 (SD 3. 7)% from T(6m) to T(12m) (P < 0.05). Mean fat mass (m(f), from bioelectrical impedance analysis measurements) tended to decrease [-2.0 (SD 4.2)%, P = 0.10] during the training period but increased by 7.8 (SD 10.9)% between T(6m) and T(12m) (P < 0.05). The mean fat free mass did not vary during the study period (P = 0.81) but magnetic resonance imaging (MRI) showed that mean thigh muscle volume decreased between T(7w) and T(12m) to less than at T(o) [T(12m) - T(o) = -2.3 (SD 3.6)%, P = 0.05]. Therefore, this study confirmed the favourable effects of endurance training on the physical capacity and body composition of elderly people, but demonstrated that the training programme would have to be continued to maintain the training-related benefits (i.e. increased VO(2max) and Wdot(max)) which would otherwise be lost within 1 year. After training, m(b) and m(f) were found to be increased. Furthermore, a fast and reproducible MRI protocol was validated for study of small intra-individual variations in tissue volumes in longitudinal studies.

Giant cell tumour of the hamate. Case report.

We report the case of a 31-year-old woman who had had the distal end of the ulna resected for a giant cell tumour five years before presenting with a further one in the hamate. The medullary cavity of the hamate was curetted and cancellous bone grafted from the distal radius. Her symptoms resolved, and 26 months postoperatively the cortex of the hamate was fully restored.

Vasopressin stimulates tyrosine phosphorylation by activation of PKC in the rat smooth muscle cell line, A-10.

Arginine vasopressin (AVP)-induced tyrosine phosphorylation was studied in a rat smooth muscle cell line, A-10, by western blotting, using a monoclonal antibody against phosphotyrosine. AVP stimulated the phosphorylation of several cellular proteins of molecular mass 60-130 kDa in a time- and dose-dependent manner. Phosphorylation was mediated largely by V(1)receptor subtype since it was inhibited by selective V(1)antagonist and was only partially elicited by the V(2)agonist, desmopressin. Heterotrimeric G-proteins seemed to be involved in the phosphorylation mechanism because fluoraluminates, an activator of heterotrimeric G-proteins (and thus an uncoupler of the receptor-G-protein interaction) inhibited the AVP-induced phosphorylation. The protein kinase C (PKC) inhibitors: staurosporine, H7 and GF109203X are able to block the AVP-stimulated phosphorylation. The last of these has been shown to be one of the most selective inhibitors of PKC. These results indicate that PKC is upstream of the phosphorylation, a motion which is supported by the fact that the AVP-stimulated phosphorylation was downregulated by phorbol esters.

[D/D genotype of the gene for angiotensin converting enzyme as a risk factor for post-stent coronary restenosis]. / El genotipo D/D del gen de la enzima conversiva de la angiotensina como factor de riesgo de reestenosis post-stent coronario.

INTRODUCTION: Although intracoronary stenting has decreased restenosis rate compared to percutaneous balloon angioplasty, still a high number of patients develop in-stent restenosis, which is an entity primarily due to tissue proliferation. Experimental studies have indicated that the renin-angiotensin system is involved in neointimal hyperplasia. Plasma and cellular levels of ACE are associated with an I/D polymorphism in the ACE gene. Indeed, DD subjects have the higher ACE levels. The purpose of this study was to explore the possibility that the I/D polymorphism might be related with in-stent restenosis. METHODS: We studied the ACE polymorphism in 48 consecutive patients who underwent successful implantation of an elective coronary stent in native coronary vessels and had a 6 month angiographic follow up. Restenosis (50% of the reference vessel) was observed in 23/48 patients. Patients with or without restenosis did not differ in demographic or clinical variables like diabetes, plasma cholesterol levels or in quantitative angiographic parameters such as vessel reference size or minimal lumen diameter after stent implantation. RESULTS: I/D polymorphism was distributed as follows: 22.9% of the patients were D/D; 14.5% were I/I and 62.5% of the patients were heterozygous I/D. The presence of restenosis was strongly related with the I/D polymorphism: 81.8% of the patients with D/D genotype had restenosis, compared with 40.0% of I/D patients and only 14.2% of the I/I patients (chi 2 p < 0.01). CONCLUSIONS: In this limited cohort, homocygous D/D of the ACE gene was significantly associated with in-stent restenosis, whereas restenosis was infrequent in patients with the I/I genotype.