RHBDD2 overexpression promotes a chemoresistant and invasive phenotype to rectal cancer tumors via modulating UPR and focal adhesion genes.

The current standard of care for locally advanced rectal cancer (RC) is neoadjuvant radio-chemotherapy (NRC) with 5-fluorouracil (5Fu) as the main drug, followed by surgery and adjuvant chemotherapy. While a group of patients will achieve a pathological complete response, a significant percentage will not respond to the treatment. The Unfolding Protein Response (UPR) pathway is generally activated in tumors and results in resistance to radio-chemotherapy. We previously showed that RHBDD2 gene is overexpressed in the advanced stages of colorectal cancer (CRC) and that it could modulate the UPR pathway. Moreover, RHBDD2 expression is induced by 5Fu. In this study, we demonstrate that the overexpression of RHBDD2 in CACO2 cell line confers resistance to 5Fu, favors cell migration, adhesion and proliferation and has a profound impact on the expression of both, the UPR genes BiP, PERK and CHOP, and on the cell adhesion genes FAK and PXN. We also determined that RHBDD2 binds to BiP protein, the master UPR regulator. Finally, we confirmed that a high expression of RHBDD2 in RC tumors after NRC treatment is associated with the development of local or distant metastases. The collected evidence positions RHBDD2 as a promising prognostic biomarker to predict the response to neoadjuvant therapy in patients with RC.

Phase stability and electronic structure of iridium metal at the megabar range.

The 5d transition metals have attracted specific interest for high-pressure studies due to their extraordinary stability and intriguing electronic properties. In particular, iridium metal has been proposed to exhibit a recently discovered pressure-induced electronic transition, the so-called core-level crossing transition at the lowest pressure among all the 5d transition metals. Here, we report an experimental structural characterization of iridium by x-ray probes sensitive to both long- and short-range order in matter. Synchrotron-based powder x-ray diffraction results highlight a large stability range (up to 1.4 Mbar) of the low-pressure phase. The compressibility behaviour was characterized by an accurate determination of the pressure-volume equation of state, with a bulk modulus of 339(3) GPa and its derivative of 5.3(1). X-ray absorption spectroscopy, which probes the local structure and the empty density of electronic states above the Fermi level, was also utilized. The remarkable agreement observed between experimental and calculated spectra validates the reliability of theoretical predictions of the pressure dependence of the electronic structure of iridium in the studied interval of compressions.

Stability and nature of the volume collapse of ε-Fe2O3 under extreme conditions.

Iron oxides are among the major constituents of the deep Earth's interior. Among them, the epsilon phase of Fe2O3 is one of the less studied polymorphs and there is a lack of information about its structural, electronic and magnetic transformations at extreme conditions. Here we report the precise determination of its equation of state and a deep analysis of the evolution of the polyhedral units under compression, thanks to the agreement between our experiments and ab-initio simulations. Our results indicate that this material, with remarkable magnetic properties, is stable at pressures up to 27 GPa. Above 27 GPa, a volume collapse has been observed and ascribed to a change of the local environment of the tetrahedrally coordinated iron towards an octahedral coordination, finding evidence for a different iron oxide polymorph.

Evolution of magnetoelectric properties of Sc-diluted TbMnO3.

The magnetoelectric properties of the TbMn(1-x)Sc(x)O3 series have been studied at low temperatures by means of heat capacity, magnetic measurements and impedance spectroscopy. TbMnO3 exhibits as expected three transitions upon lowering the temperature corresponding to the magnetic ordering of the two sublattices (Mn and Tb) and the ferroelectric transition. Ferroelectricity disappears with Sc dilution for x > 0.1 because the non-collinear magnetic arrangement is destroyed. The dilution of Mn with a non-magnetic ion is also detrimental to the magnetic ordering of both Mn and Tb sublattices. The system evolves to a magnetic glassy state for the intermediate compositions. Formal TbScO3 shows Sc-deficiency and long range magnetic ordering of Tb(3+) moments in the ab-plane brought by the direct interaction between Tb(3+) ions. This ordering is different from the one found in TbMnO3 due to the lack of magnetic coupling between Tb- and Mn-sublattices. A small substitution of Sc by Mn in TbScO3 destroys the Tb ordering giving rise to a magnetic glass behaviour. This effect is ascribed to the partial polarization of Tb sublattice by the paramagnetic Mn which competes with the direct Tb-Tb exchange.

Enhancement of ferromagnetic correlations on multiferroic TbMnO3 by replacing Mn with Co.

The structural, electronic and magnetic properties of TbMn(1-x)Co(x)O(3) (0.1 ≤ x ≤ 0.9) compounds are reported. The samples are isostructural to TbMnO(3) adopting the orthorhombic distorted perovskite structure (Pbnm), except for x = 0.4, 0.5 and 0.6, where an ordered double perovskite structure (P2(1)/n) is found. X-ray absorption spectra at the Mn and Co K edges show an incomplete charge transfer between Mn and Co atoms yielding a mixed valence state Mn(3+)/Mn(4+) and Co(3+)/Co(2+) for the whole series. Neutron powder diffraction measurements show the development of a ferromagnetic ground state for the intermediate compositions (0.3 ≤ x ≤ 0.6) indicating that the ferromagnetic superexchange Mn(4+)-O-Co(2+) interaction is the strongest among a wide set of competitive interactions. The ferromagnetic ordering is, however, not fully achieved and coexists with glassy magnetic properties. With increasing concentration of Co (x ≥ 0.7) the long range ordering vanishes and only a glassy magnetic behavior with slow dynamics is found. These properties could be related to the existence of magnetically inhomogeneous small clusters arising from competitive magnetic interactions.

Structural properties of Pb2MnW(1-x)Re(x)O6 double perovskites.

Pb2MnW(1-x)Re(x)O6 samples have been synthesized and their structure determined by powder x-ray diffraction. These samples undergo a first order structural phase transition between 413 and 445 K depending on the composition. Above this temperature, the samples are cubic. Below the transition temperature, solid solutions are found for x ≤ 0.2 and x ≥ 0.5. The W-rich samples adopt an orthorhombic cell whereas the Re-rich compounds are monoclinic. In the intermediate region, 0.2 < x < 0.5, both phases coexist. X-ray absorption spectra did not reveal significant changes in the local structure for Pb, Mn or Re atoms across the structural phase transition. All the atoms exhibit distorted environments in the whole series. In the case of Pb and W(Re) atoms, the local distortion remains in the high temperature phase. Samples with x ≤ 0.2 also show a sharp discontinuity in the dielectric permittivity at the phase transition temperature indicating the presence of a concomitant electrical ordering in the bulk grains. Such an anomaly in the dielectric constant is not observed for the x ≥ 0.5 samples, compatible with the lack of dipole ordering for this composition range. The different electrical behaviours also explain the differences in the entropy content for the two types of transition.

The transition from ferromagnet to cluster-glass in La(1-x)Tb(x)Mn1/2Sc1/2O3.

We report the structural and magnetic properties of the La(1-x)Tb(x)Mn(1/2)Sc(1/2)O(3) series. LaMn(1/2)Sc(1/2)O(3) shows a long range ferromagnetic ordering in agreement with a fully polarized Mn-sublattice. The substitution of La with Tb produces structural changes which affect the magnetic properties. This substitution leads to a contraction in the unit cell volume that mainly reduces the M-O-M bond angle (M = Mn, Sc). The bending of this angle decreases the Mn-O-Mn superexchange interaction and enhances the competition between nearest-neighbour and next-nearest-neighbour interactions. Accordingly, the magnetic ground state changes from ferromagnetic to a glassy magnetic state. Large thermal irreversibility between zero-field-cooled and field-cooled conditions is observed for all samples. The study of the dynamic magnetic properties has been performed using the frequency dependent real part of the ac magnetic susceptibility. The use of both the Vogel-Fulcher law and the conventional critical slowing down law yields similarly good accuracies in the fits. The relaxation times obtained from both laws concur with the existence of a cluster-glass for x ≥ 0.5 samples.

Origin of the pre-peak features in the oxygen K-edge x-ray absorption spectra of LaFeO3 and LaMnO3 studied by Ga substitution of the transition metal ion.

We report on experimental oxygen K-edge x-ray absorption near edge structure (XANES) spectra of the LaFe(1 - x)Ga(x)O(3) and LaMn(1 - x)Ga(x)O(3) series. Transition metal substitution by the 3d full shell Ga atom is mainly reflected in a systematic decrease of the pre-edge structures in the XANES spectra of the two series. This result shows that the associated states originate from the hybridization of oxygen 2p and unoccupied Fe (or Mn) 3d states. In order to gain insight into the states associated with the pre-edge spectral features, we have performed ab initio theoretical calculations based on multiple scattering theory. Simulations with variable cluster size and composition around the absorber oxygen in the LaFeO(3) and LaMnO(3) crystal structures were carried out. We find that the low-energy pre-peak is reproduced once the absorbing oxygen and the two nearest neighbour Fe (or Mn) ions are considered in the cluster. Conversely, higher energy pre-peaks only arise when the full oxygen coordination geometry around the two metal sites is taken into account, implying that their energy distance is a reflection of the strength of the oxygen ligand field. Substitutions of the two nearest neighbours by Ga atoms in the cluster of calculation lead to changes in the theoretical spectra that reasonably agree with the evolution of the pre-peaks in the experimental XANES spectra of both the series.

Caso de abdomen presentado en la Sesión General de Lectura de Casos del XXX Congreso Nacional de la SERAM, A Coruña. Mayo 2010 / No disponible

No disponible

Tratamiento quirúrgico de la obesidad mediante “banda gástrica ajustable” por vía la paroscópica. Una técnica posible en los programas de CMA / No disponible

Objetivo: Exponer nuestra experiencia en el tratamiento quirúrgico de la obesidad mediante banda gástrica ajustable por la paroscopia (BGAL) dentro de un programa de cirugía de corta estancia. Pacientes y método: Entre junio de 2006 y diciembre de2007 fueron intervenidos de forma consecutiva 57 pacientes obesos mediante la técnica de BGAL. Los criterios de selección utilizados para establecer la indicación quirúrgica se basan en los establecidos por el Instituto Nacional de Salud americano y en la declaración de Salamanca de la Sociedad Española de Cirugía de la Obesidad (SECO). Las variables analizadas son: tiempo quirúrgico, tiempo de cumplimiento de criterios de alta en CMA, tiempo de estancia postoperatoria, tiempo de estancia total (desde el ingreso hasta el alta) y complicaciones. Resultados: Todos los pacientes fueron dados de alta dentro de las 24 horas postoperatorias. La estancia hospitalaria postoperatoria fue de 13 horas (11-20). La estancia media total fue de 20 horas (con una noche). El tiempo medio de cumplimiento de los criterios de alta fue de 6 horas. El tiempo quirúrgico medio fue de 118 minutos (80-164). No se registró ninguna complicación intraoperatoria. No hubo reconversiones, reintervenciones, reingresos o complicaciones en los 30 primeros días postoperatorios. Hubo un caso de rotación del reservorio subcutáneo, que obligó a reposición amiento bajo anestesia local, así como tres disfunciones esofágicas. Conclusiones: La intervención de BGAL, realizada por equipos multidisciplinares dedicados específicamente a la obesidad mórbida, puede desarrollarse dentro de programas de cirugía de corta estancia y CMA. La mayoría de pacientes cumplen los criterios de alta en las 6 primeras horas postoperatorias (AU)

Objective: To show our experience in the laparoscopic surgical treatment of obesity using the adjustable gastric band (AGBL) included in a program for day surgery .Patients and method: Between June 2006 and December 2007 we performed the procedure on 57 obese patients, consecutively, using the AGBL technique. The selection criteria used to establish the surgical indications is based on the American National Institute of Health and the SECO. The variables analyzed were: surgical time, time until discharge criteria are met, time spent in hospital post surgery, the overall time of hospital stay (from admittance until leaving) and complications. Results: All patients were discharged within 24 hours postsurgery. The hospital postoperative stay was 13 hours (r:11-20 h). The total average period of time spent in the hospital was 20 hours (with one night). Average time before reaching discharge criteria was 6 hours. Average surgical time was 118 min (r:80-164 m). We have not registered any intra-operative complications. No reconversions. No re-operations No re-admissions to hospital. No complications during the first 30 day spost surgery. 1 case of subcutaneous port rotation of reservoir that required a repositioning under local anesthesia. 3 esophageal disfuntions. Conclusions: The AGBL procedure performed by multidisciplinary teams dedicated specifically to the treatment of morbid obesity can be included in a program for ambulatory surgery. Most patients recover and are discharged before the anticipated 6 postsurgical hours (AU)

[Retrorectal cystic hamartoma (tailgut cyst): radiologic and pathologic findings]. / Hamartoma quístico retrorrectal: hallazgos radiopatológicos.

Cystic hamartoma is a rare congenital lesion that presents as a presacral mass. It arises from remnants of the embryonic postanal gut. It is more common in women and usually presents in middle age. It is usually asymptomatic. It is difficult to distinguish the imaging appearance of cystic hamartoma from that of many other presacral cysts; therefore, histologic analysis is essential for the definitive diagnosis. Complete surgical excision is indicated to establish the diagnosis and avoid complications (infection and malignant transformation).

Hamartoma quístico retrorrectal: hallazgos radiopatológicos / Retrorectal cystic hamartoma (tailgut cyst): Radiologic and pathologic findings

El hamartoma quístico retrorrectal es una rara lesión congénita que suele presentarse como una masa presacra. Se origina a partir de restos del intestino caudal embrionario. Es más frecuente en mujeres y generalmente se diagnostica en la edad media. Suele ser asintomático. Radiológicamente puede ser indistinguible de otras lesiones quísticas que también pueden presentarse en la región presacra, por lo que el examen histológico de la pieza resulta imprescindible para su diagnóstico definitivo. El tratamiento quirúrgico es fundamental para establecer el diagnóstico y para evitar complicaciones (infección y degeneración maligna) (AU)

Cystic hamartoma is a rare congenital lesion that presents as a presacral mass. It arises from remnants of the embryonic postanal gut. It is more common in women and usually presents in middle age. It is usually asymptomatic. It is difficult to distinguish the imaging appearance of cystic hamartoma from that of many other presacral cysts; therefore, histologic analysis is essential for the definitive diagnosis. Complete surgical excision is indicated to establish the diagnosis and avoid complications (infection and malignant transformation) (AU)

Ablación por radiofrecuencia de lesiones malignas pulmonares guiada por tomografía computarizada. Experiencia preliminar / CT-guided radiofrequency ablation of malignant pulmonary lesion: preliminary experience

Objetivo: Describir las experiencias preliminares de la técnica de ablación por radiofrecuencia (ARF) de lesiones malignas pulmonares guiada mediante tomografía computarizada (TC). Material y métodos: Se presentan tres casos realizados en dos hospitales de tercer nivel. Dos pacientes tenían un carcinoma primitivo de pulmón, mientras que el tercero presentaba una metástasis solitaria de hipernefroma. Se describen las indicaciones, la técnica del procedimiento y las posibles complicaciones. Resultados: Se pudo realizar el procedimiento en los tres pacientes. En ningún caso se produjo una complicación importante que impidiera la práctica de la técnica. En dos pacientes se realizaron controles posteriores mediante TC que mostraban respuesta al tratamiento. Conclusión: La ARF de lesiones malignas pulmonares guiada mediante TC es una técnica mínimamente invasiva que puede ser una alternativa al tratamiento estándar en casos seleccionados

Objective: To describe our preliminary experience in the technique of CT-guided radiofrequency ablation (RFA) of malignant pulmonary lesions. Material and methods: We present three cases treated at two tertiary healthcare centers. Two patients had primary lung carcinomas and the third had a single lung metastasis from a hypernephroma. We describe the indications for this procedure, technical aspects of the procedure, and possible complications. Results: The procedure was successfully performed in all three patients. No significant complications that might impede the procedure were observed in any case. Two patients underwent follow-up CT to evaluate the response to the treatment. Conclusion: CT-guided RFA of malignant lung lesions is a minimally invasive technique that can be used as an alternative to standard treatment in selected cases

Color Doppler image of central retinal artery of eyes with an intraconal mass.

PURPOSE: Retinal ischemia secondary to hypoperfusion of the central retinal artery is recognized as one factor that may contribute to the development of loss of vision in eyes with intraorbital tumors. We study intraorbital tumors which produce motility disturbances and visual problems by color Doppler imaging to evaluate this factor. METHODS: We examined the central retinal artery velocities of 3 patients with disc edema caused by intraconal masses (2 cavernous hemangiomas and 1 presumed optic nerve glioma) via color Doppler imaging. RESULTS: The time-velocity waveform demonstrated abnormally high vascular resistance in the central retinal artery of all affected eyes in the primary position compared with the normal waveform seen in the other eyes. We compared the pulsatility index of eyes with an intraconal mass and contralateral, control eyes using Student's t test for paired samples and significant differences were noted between both groups (p< 0.01). CONCLUSIONS: Intraconal tumors could produce increased pressure in the optic nerve sheath and the optic nerve tissue which could be associated with impaired retinal and optic nerve blood flow and the subsequent amaurosis encountered with intraorbital tumors.

Endogenous endophthalmitis caused by Rickettsia conorii.

PURPOSE: We report herein the first confirmed case of endogenous endophthalmitis caused by Rickettsia conorii. METHODS: Indirect immunofluorescence was performed in peripheral blood with antibodies against Rickettsia conorii. A vitreous aspirate was studied by indirect immunofluorescence with antibodies against Rickettsia conorii and by direct immunofluorescence with conjugated antigen against Rickettsia conorii. RESULTS: Indirect immunofluorescence in peripheral blood gave a titre of 1/320 at that moment and 1/640 fifteen days later. The vitreous aspirate studied by indirect immunofluorescence gave a titre of 1/620 and it showed a positive reaction to Rickettsia conorii antigen by direct immunofluorescence. CONCLUSION: Rickettsia conorii should be considered in the differential diagnosis of endogenous endophthalmitis in areas where Mediterranean spotted fever is endemic.

[Color Doppler echography study of ocular blood flow velocity in patients with proliferative diabetic retinopathy after performance of retinal pan-photocoagulation: 2 years' follow-up]. / Estudio mediante ecografía Doppler color de las velocidades de flujo sanguíneo ocular en pacientes afectos de retinopatía diabética proliferante tras la realización de panfotocoagulación retiniana: dos años de seguimiento.

PURPOSE: Color Doppler imaging allows for simultaneous two-dimensional anatomical imaging and Doppler measurement of blood flow velocity. Because hemodynamic changes have been seen in diabetic patients after photocoagulation by other techniques, the authors compared 25 eyes with proliferative diabetic retinopathy before, 6 months, 1 year, and 2 years after panretinal photocoagulation with a matched control group of 30 healthy volunteers. METHODS: The ophthalmic artery, short posterior ciliary artery, central retinal vessels and vortex veins of all patients were examined, and the systolic, diastolic and mean arterial velocities were measured. Panretinal photocoagulation was performed with these parameters: 800-1000 spots, 0.1s, 500 micron argon laser. RESULTS: Student's t test revealed that the perfusion velocity was significantly lower in diabetic patients than in normals (Vsystolic in the ophthalmic artery: 31.7 (6.7) cm/s vs 36.6 (7.0) cm/s, respectively, P = 0.03). After treatment, blood flow velocities were significantly lower than before photocoagulation (Vsystolic in the ophthalmic artery: 6 months after treatment 26.9 (7.2) cm/s, P = 0.018 and 1 year after photocoagulation 25.5 (7.0) cm/s, P = 0.009; and 2 years after photocoagulation, 25.7 (6.8) cm/s, P = 0.01). No statistically significant differences were found between 6 months, 1 year, and 2 years after panretinal photocoagulation. No significant correlations were found between age and blood velocities in diabetics and healthy volunteers. CONCLUSIONS: Eyes with proliferative diabetic retinopathy showed lower ocular perfusion velocities than normals. Photocoagulation resulted in a reduction in ocular blood flow velocities; these values did not change during 2 years of follow-up.

Ocular blood flow velocities in patients with proliferative diabetic retinopathy after scatter photocoagulation. Two years of follow-up.

PURPOSE: Color Doppler imaging allows for simultaneous two-dimensional anatomic imaging and Doppler measurement of blood flow velocity. Because hemodynamic changes have been seen in diabetic patients after photocoagulation by other techniques, the authors compared 25 eyes with proliferative diabetic retinopathy before, 6 months after, 1 year after, and 2 years after panretinal photocoagulation with a matched control group of 30 healthy volunteers (55 eyes). METHODS: The ophthalmic artery, short posterior ciliary artery, central retinal vessels, and vortex veins of all patients were examined, and the systolic, and diastolic, and mean arterial velocities were measured. Panretinal photocoagulation was performed with these parameters: 800-1000 spots, 0.1 second, 500-microns argon laser. RESULTS: Student's t test revealed that the perfusion velocity was significantly lower in diabetic patients than in healthy controls (V systolic in the ophthalmic artery: 31.7 +/- 6.7 cm/s vs. 36.6 +/- 7.0 cm/s, respectively, P = 0.03). After treatment, blood flow velocities were significantly lower than before photocoagulation (V systolic in the ophthalmic artery: 6 months after treatment, 26.9 +/- 7.2 cm/s, P = 0.018; 1 year after photocoagulation, 25.5 +/- 7.0 cm/s, P = 0.009; and 2 years after photocoagulation, 25.7 +/- 6.8 cm/s, P = 0.01). No statistically significant differences were found between 6 months, 1 year, and 2 years after panretinal photocoagulation. No significant correlations were found between patient age and blood velocities in diabetics and healthy volunteers. CONCLUSIONS: Eyes with proliferative diabetic retinopathy showed lower ocular perfusion velocities than controls. Photocoagulation resulted in a reduction in ocular blood flow velocities; these values did not change during 2 years of follow-up.

Ocular blood flow velocities in patients with proliferative diabetic retinopathy before and after scatter photocoagulation: a prospective study.

INTRODUCTION: Color Doppler imaging allows for simultaneous two-dimensional anatomical imaging and Doppler measurement of blood flow velocity. Chemicals are released during the development of a thermal lesion caused by photocoagulation. METHODS: A prospective study compared ocular blood flow velocities (ophthalmic artery, posterior ciliary arteries, central retinal artery, central retinal vein and vortex veins) before and 30 minutes after the first episode of scatter photocoagulation (650, 0.1 s, 500 microns argon laser) in 25 patients with proliferative diabetic retinopathy, using a color Doppler imaging unit (Toshiba Sonolayer SSA-270 A with a 5.0 MHz PLF-503 ST phased-array scanning head). RESULTS: Systolic, diastolic and mean arterial blood flow velocities were higher after photo-coagulation than before. There was a significant difference in the ophthalmic artery; diastolic (P < 0.01), mean velocity (P < 0.05), posterior ciliary arteries; systolic (P < 0.01), diastolic (P < 0.001), mean velocity (P < 0.05), central retinal artery; mean velocity (P < 0.05), central retinal vein; systolic (P < 0.001) and vortex veins; systolic (P < 0.01), diastolic (P < 0.01). Ophthalmic artery systolic and end-diastolic velocities declined with age in diabetic patients before scatter photocoagulation; these changes were not significant (systolic: r = -0.33, diastolic: r = -0.30). DISCUSSION: During and after thermal lesion caused by photocoagulation, there is a dynamic inflammatory and an autoregulatory response of the retinal circulation, causing changes in the ocular circulation.