Observation of room-temperature polar skyrmions.

Complex topological configurations are fertile ground for exploring emergent phenomena and exotic phases in condensed-matter physics. For example, the recent discovery of polarization vortices and their associated complex-phase coexistence and response under applied electric fields in superlattices of (PbTiO3)n/(SrTiO3)n suggests the presence of a complex, multi-dimensional system capable of interesting physical responses, such as chirality, negative capacitance and large piezo-electric responses1-3. Here, by varying epitaxial constraints, we discover room-temperature polar-skyrmion bubbles in a lead titanate layer confined by strontium titanate layers, which are imaged by atomic-resolution scanning transmission electron microscopy. Phase-field modelling and second-principles calculations reveal that the polar-skyrmion bubbles have a skyrmion number of +1, and resonant soft-X-ray diffraction experiments show circular dichroism, confirming chirality. Such nanometre-scale polar-skyrmion bubbles are the electric analogues of magnetic skyrmions, and could contribute to the advancement of ferroelectrics towards functionalities incorporating emergent chirality and electrically controllable negative capacitance.

Local negative permittivity and topological phase transition in polar skyrmions.

Topological solitons such as magnetic skyrmions have drawn attention as stable quasi-particle-like objects. The recent discovery of polar vortices and skyrmions in ferroelectric oxide superlattices has opened up new vistas to explore topology, emergent phenomena and approaches for manipulating such features with electric fields. Using macroscopic dielectric measurements, coupled with direct scanning convergent beam electron diffraction imaging on the atomic scale, theoretical phase-field simulations and second-principles calculations, we demonstrate that polar skyrmions in (PbTiO3)n/(SrTiO3)n superlattices are distinguished by a sheath of negative permittivity at the periphery of each skyrmion. This enhances the effective dielectric permittivity compared with the individual SrTiO3 and PbTiO3 layers. Moreover, the response of these topologically protected structures to electric field and temperature shows a reversible phase transition from the skyrmion state to a trivial uniform ferroelectric state, accompanied by large tunability of the dielectric permittivity. Pulsed switching measurements show a time-dependent evolution and recovery of the skyrmion state (and macroscopic dielectric response). The interrelationship between topological and dielectric properties presents an opportunity to simultaneously manipulate both by a single, and easily controlled, stimulus, the applied electric field.

Phase coexistence and electric-field control of toroidal order in oxide superlattices.

Systems that exhibit phase competition, order parameter coexistence, and emergent order parameter topologies constitute a major part of modern condensed-matter physics. Here, by applying a range of characterization techniques, and simulations, we observe that in PbTiO3/SrTiO3 superlattices all of these effects can be found. By exploring superlattice period-, temperature- and field-dependent evolution of these structures, we observe several new features. First, it is possible to engineer phase coexistence mediated by a first-order phase transition between an emergent, low-temperature vortex phase with electric toroidal order and a high-temperature ferroelectric a1/a2 phase. At room temperature, the coexisting vortex and ferroelectric phases form a mesoscale, fibre-textured hierarchical superstructure. The vortex phase possesses an axial polarization, set by the net polarization of the surrounding ferroelectric domains, such that it possesses a multi-order-parameter state and belongs to a class of gyrotropic electrotoroidal compounds. Finally, application of electric fields to this mixed-phase system permits interconversion between the vortex and the ferroelectric phases concomitant with order-of-magnitude changes in piezoelectric and nonlinear optical responses. Our findings suggest new cross-coupled functionalities.

Electrostatic coupling and local structural distortions at interfaces in ferroelectric/paraelectric superlattices.

The performance of ferroelectric devices is intimately entwined with the structure and dynamics of ferroelectric domains. In ultrathin ferroelectrics, ordered nanodomains arise naturally in response to the presence of a depolarizing field and give rise to highly inhomogeneous polarization and structural profiles. Ferroelectric superlattices offer a unique way of engineering the desired nanodomain structure by modifying the strength of the electrostatic interactions between different ferroelectric layers. Through a combination of X-ray diffraction, transmission electron microscopy, and first-principles calculations, the electrostatic coupling between ferroelectric layers is studied, revealing the existence of interfacial layers of reduced tetragonality attributed to inhomogeneous strain and polarization profiles associated with the domain structure.

Could thymoglobulin increase hemorrhagic risk in the perioperative transplantation period of sensitized kidney recipients?

OBJECTIVE: It has been described that thymoglobulin could increase the risk of infections and malignancies, in comparison to basiliximab. Leukopenia and thrombocytopenia are also more common within the first days after transplantation among thymoglobulin patients. Our objective was to analyze bleeding complications in this subset of patients. MATERIAL AND METHODS: Bleeding complications were evaluated among 515 renal transplants carried out at our institution between 2012 and 2018. We compared patients treated with thymoglobulin (Group 1, N=91) with those treated with basiliximab (Group 2, N=424). RESULTS: We found differences in platelet decrease: 95,142.2 (55,339.6) in Group 1 and 52,364.3 (69,116.6) in Group 2 (P=0.001), number of patients with severe thrombocytopenia (<75,000/mm3) (20.8% vs. 3.7%, P=0.001), number of blood units transfused (3.25 (0.572) vs. 2.2 (0.191, P=0.028) and percentage of patients that required surgery due to bleeding (18.2% vs. 7.7%, P=0.046). In a multiple lineal regression multivariable analysis (dependent variable was number of blood units transfused), only age [OR 0.037, 95% CI (0.003-0.070)] and type of immunosuppression [OR 1.592, 95% CI (1.38-2.84)] showed statistical significance. CONCLUSIONS: The use of thymoglobulin in the perioperative transplantation period could increase bleeding complications. In our series, in the group of patients with thymoglobulin, severe thrombocytopenia was 6 times more frequent, and active bleeding that required surgery was also 2.5 times more frequent. One way to continue with the use of this immunosuppression agent, might be to adjust the dose instead of discontinuing it. The use of thymoglobulin should be a factor to consider in the postoperative period of these patients.

Concomitant intraductal carcinoma of the prostate and response to hormonal therapy in metastatic prostate carcinoma.

INTRODUCTION AND OBJECTIVE: Most prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini. We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients. PATIENTS AND METHODS: We retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P. RESULTS: Mean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (P = .007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (P = .05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (P = .001). In the multivariate analysis, adenocarcinoma subtype was statistically significant P .014, CI 95% (HR 0.058, 0.006-0.56) CONCLUSIONS: IDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. Once IDC-P is identified, clinicians could extrapolate the relative poor response to hormonal therapy. Consequently, follow-up of these patients in this scenario should be more strict.

Pseudo-Jahn-Teller origin of the low barrier hydrogen bond in N(2)H(7) (+).

The microscopic origin and quantum effects of the low barrier hydrogen bond (LBHB) in the proton-bound ammonia dimer cation N(2)H(7) (+) were studied by means of ab initio and density-functional theory (DFT) methods. These results were analyzed in the framework of vibronic theory and compared to those obtained for the Zundel cation H(5)O(2) (+). All geometry optimizations carried out using wavefunction-based methods [Hartree-Fock, second and fourth order Moller-Plesset theory (MP2 and MP4), and quadratic configuration interaction with singles and doubles excitations (QCISD)] lead to an asymmetrical H(3)N-H(+)cdots, three dots, centeredNH(3) conformation (C(3v) symmetry) with a small energy barrier (1.26 kcalmol in MP4 and QCISD calculations) between both equivalent minima. The value of this barrier is underestimated in DFT calculations particularly at the local density approximation level where geometry optimization leads to a symmetric H(3)Ncdots, three dots, centeredH(+)cdots, three dots, centeredNH(3) structure (D(3d) point group). The instability of the symmetric D(3d) structure is shown to originate from the pseudo-Jahn-Teller mixing of the electronic (1)A(1g) ground state with five low lying excited states of A(2u) symmetry through the asymmetric alpha(2u) vibrational mode. A molecular orbital study of the pseudo-Jahn-Teller coupling has allowed us to discuss the origin of the proton displacement and the LBHB formation in terms of the polarization of the NH(3) molecules and the transfer of electronic charge between the proton and the NH(3) units (rebonding). The parallel study of the H(5)O(2) (+) cation, which presents a symmetric single-well structure, allows us to analyze why these similar molecules behave differently with respect to proton transfer. From the vibronic analysis, a unified view of the Rudle-Pimentel three-center four-electron and charge transfer models of LBHBs is given. Finally, the large difference in the N-N distance in the D(3d) and C(3v) configurations of N(2)H(7) (+) indicates a large anharmonic coupling between alpha(2u)-alpha(1g) modes along the proton-transfer dynamics. This issue was explored by solving numerically the vibrational Schrodinger equation corresponding to the bidimensional E[Q(alpha(2u)),Q(alpha(1g))] energy surface calculated at the MP46-311++G(**) level of theory.

The SIESTA method; developments and applicability.

Recent developments in and around the SIESTA method of first-principles simulation of condensed matter are described and reviewed, with emphasis on (i) the applicability of the method for large and varied systems, (ii) efficient basis sets for the standards of accuracy of density-functional methods, (iii) new implementations, and (iv) extensions beyond ground-state calculations.

[Presentation of a new case of primary clear cell adenocarcinoma of the urethra and its surgical management]. / Presentación de un nuevo caso de adenocarcinoma de células claras uretral y su manejo quirúrgico.

OBJECTIVE: To present a new case of a primary clear cell adenocarcinoma of the urethra and its surgical management. MATERIAL AND METHODS: We describe the clinical, diagnosis, treatment and development of this kind of tumor. Review of the literature. CONCLUSIONS: It is an unusual type of cancer associated with poor prognosis. Currently the construction of a continent urinary diversion using the Mitrofanoff principle has many indications as our case. Laparoscopic radical cystectomy can be done by experienced groups without adding much more technical difficulties; there are no long-term oncological outcome data but we believe in some functional advantages.

[Brachyterapy in localized prostate cancer]. / Braquiterapia en el cáncer de próstata localizado.

INTRODUCTION AND OBJECTIVES: Considering the high frequency of localized prostate cancer in stages, at the moment there are minimally invasive techniques that compete with the classic surgery. One of them is the Low Dose Rate (LDR) Brachytherapy with permanent implants of 1125 seeds. The objective of the present study is to expose our experience from the year 1998, when we made the first treatment, until today. The results and the morbidity of the patients over a 7 and a half years period are analyzed. MATERIAL AND METHODS: A total of 800 patients were treated with LDR brachytherapy, with average age of 68 years and range between 48 and 83 years. In all patients the 1125 seeds were used with Rapid-Strand and peripheral load by means of intraoperative planning. RESULTS: The urinary rate of complications was of 3% of AUR, and 0.2% of urinary incontinence. The morbidity on the digestive apparatus was of a 12% intermittent bleeding, 2% of proctitis, and a 0.3% of rectal fistulas.

[Bipolar versus monopolar transurethral resection of the prostate: peroperative analysis of the results]. / Resección transuretral de próstata bipolar vs monopolar: análisis peroperatorio de los resultados.

OBJECTIVE: To analyse the differences in the postoperative period between bipolar and monopolar resection of the prostate in the endoscopic surgery of the benign prostatic hyperplasia. METHODS: 45 patients were prospectively randomized. Twenty-one underwent monopolar resection (Storz Ch 26, 30 degrees) and 24 underwent bipolar resection (Olympus ch 26, 30 degrees). RESULTS: Mean age in the bipolar group was 69,5 years versus 67,3 in the monopolar group; mean flow before surgery (7,7 ml/s vs 7,2 ml/s); ecographic prostate volume (39,5 cc vs 42,7 cc); resection volume 13 g vs 12,6 g and mean resection time was 39,7 vs 42,5 min. Cut capacity was considered notable-excellent in 90% of the patients in the bipolar group vs 50% in the monopolar group (p=0,01); adherence of fragments were considered abundant or very abundant in 0% vs 60% (p=0,01); coagulation capacity was excellent-notable in 25% vs 75% (p=0,03). There were no significant differences on the days of catheterization (2,92 vs 3,1), continuous irrigation (1,79 vs 2,05), hospitalization (3,63 vs 3,67), hematocrite descent (3,48 vs 3,32) and plasmatic sodium (0,52 vs 1,16), neither on episodes of acute urine retention (only one patient in the monopolar group). CONCLUSIONS: In our experience, TURP with SurgMaster resector in prostate smaller than 70 g offers better peroperative qualities for the surgeon (better cut capacity, less adherence of fragments) than the monopolar resection, with similar postoperative outcomes.

[Primary lymphoepithelioma-like carcinoma urinary bladder]. / Carcinoma linfoepitelioma-like puro primario de vejiga.

OBJECTIVE: To present a new case of a primary lymphoepithelioma-like carcinoma of the urinary bladder. MATERIAL AND METHODS: We describe the clinical, diagnosis, treatment and development of this kind of tumor. Review of the literature. CONCLUSIONS: It is an unusual type of bladder cancer that requires a carefully analyse from the pathologist and a confirmation by means of immunohistochemistry techniques. The focal form is associated with poor prognosis. Radical cystectomy is the gold standard. This kind of tumor has sensibility to chemo and radiotherapy, who can be used as adjuvant therapy.

[Renal hydatidic cyst simulating hypernephroma]. / Quiste hidatídico renal simulando hipernefroma.

OBJECTIVE: To present a new case of hydatid cyst of the kidney with a difficult radiographic diagnosis. MATERIAL AND METHODS: We describe the clinical, diagnosis and treatment of a complex renal mass and its histological confirmation after surgery. Review of the literature. CONCLUSIONS: kidney's hydatidose is an unusual placement of this pathology. It is important to take care in the differential diagnosis in the context of complexes renal masses. There are some diagnosis procedures which can help us to establish it. Surgery is the treatment of choice in the majority of the cases.

Retroperitoneal and transperitoneal laparoscopic cryotherapy for small renal masses.

OBJECTIVE: Cryotherapy is a minimally invasive ablative technique that is considered an alternative to conventional surgery for preserving renal function in small renal tumors and in selected cases. We present our results from laparoscopic renal cryotherapy. MATERIAL AND METHOD: We retrospectively analyzed 17 renal tumors diagnosed in 16 patients treated with cryotherapy. The patients' mean age was 66 years (43-80). The mean tumor size was 1.8cm (0.7-3.7cm). Cryotherapy with double-freeze cycle was performed laparoscopically in all cases (10 by transperitoneal approach and 7 by retroperitoneal approach). RESULTS: Perioperative biopsies were performed on all patients and were positive for malignancy in 10 cases (59%). The mean stay was 2.8 days. The mean operative time was 162 minutes. Only 1 case reverted to open surgery due to bleeding. One patient required a blood transfusion in the immediate postoperative period. The majority of complications were Clavien-Dindo grades I and II. Some 76.5% of the patients had no complications. After a mean follow-up of 31 months (6-102), 1 patient died from nontumor-related causes, and 12 patients (75%) still show no evidence of local recurrence or progression. One patient had tumor persistence and therefore underwent partial nephrectomy at 6 months. One patient had a metachronous recurrence in the same kidney at 36 months, and another patient had a recurrence at 23 months. CONCLUSIONS: Laparoscopic renal cryotherapy is a safe and feasible technique and is a good alternative to surgery for selected renal tumors.

The immobility response elicited by clamping, bandaging and grasping in the Mongolian gerbil (Meriones unguiculatus).

When grasped by the skin of the nape and lifted into the air, the young of many altricial mammals exhibit an immobility response in which they tuck their limbs against their bodies and remain inert. Such a response can be induced in the adults of some species, especially if a stronger tactile stimulus such as bandaging the head and neck or clamping the skin of the nape, is applied. In this study, the immobility response of the Mongolian gerbil (Meriones unguiculatus) is investigated, which appears to differ in potentially useful ways from other commonly studied species such as rats (Rattus norvegicus). It has been previously reported that for rats clamping or bandaging had a more profound effect on the immobility response than grasping. Mongolian gerbils were tested with all three methods (grasping, bandaging and clamping), which were repeated at intertrial intervals ranging from 3 h to 40 days. Grasping induced a significantly longer duration of immobility than either bandaging or clamping. However, repeated trials significantly increased the duration of immobility induced by clamping, whereas repeated grasping or bandaging did not do so. The marked difference in the induction of the immobility response in gerbils as compared to rats, may provide a useful model for the study of this behavior.

Potentiation by vestibular stimulation of the immobility reflex elicited by clamping in developing and adult rats.

We have previously described (Exp. Neurol., 97: 315-326, 1987) that clamping of the neck elicits a profound immobility with flexion of limbs and ventroflexion of head and neck ('carrying posture'). We also observed that when a clamped rat pup is carried by the experimenter's hand, such carrying posture was potentiated. In the present paper we observed that in adult rats vestibular stimulation by circular acceleration potentiates the duration of immobility reflex by clamping and intensifies the limb flexion. In rat pups from 10 to 20 days, vestibular stimulation potentiated only the carrying posture but not the duration of the immobility reflex by clamping.

Quantitative measurement of motor activity during the immobility reflex elicited by clamping in developing rats.

The immobility reflex can be elicited in developing rats by clamping the neck. Quantitative measurement of motor activity during such clamp-induced immobility was made by placing the rats in a jiggle cage. These measurements showed that there are two stages in the ontogenic development of this reflex; from day 5 to day 25 the inhibition of motor activity increased with age; from day 30 to day 90 the inhibition of motor activity was substantially reduced. It is postulated that in the first stage immobility could facilitate carrying by the mother whereas the second stage, when immobility is not as profound, could be related to escape from predators. Older rats must be ready to run if other strategies such as freezing and camouflage fail to avoid an attack from the predator.

Ontogeny of the endorphinergic and dopaminergic modulation on the immobility reflex elicited by clamping in rats.

The effects of some dopaminergic and endorphinergic agonists and antagonists on the immobility reflex (IR) elicited by clamping the neck of the rat were investigated. We found that both morphine and haloperidol produce a significant increase in the duration of this IR at all ages tested (10, 20 and 300 days). The effect of apomorphine depends on the age of the rat, showing an increase in the duration of the immobility reflex only at the age of 10 days which was not counteracted by haloperidol. Naloxone alone showed a slight non-significant tendency to increase the duration of the IR but blocked morphine effects at all ages tested. When naloxone was added to apomorphine there was a peculiar effect: the duration of the immobility reflex was increased significantly in rats of 20 days and adults, but not in 10-day-old rats. The combination of morphine plus haloperidol showed the most marked potentiation of the immobility reflex at all ages tested. These results are discussed with respect to the development of dopaminergic and endorphinergic systems to control posture and movement during the IR, and its possible relation to the catatonia of schizophrenics. A hypothetical model explaining an interaction between the dopaminergic and endorphinergic systems in developing and adult rats is presented.

[Gly380Arg and Asn540Lys mutations of fibroblast growth factor receptor 3 in achondroplasia and hypochndroplasia in the Spanish population]. / Análisis de las mutaciones Gly380Arg y Asn540Lys del receptor 3 del factor de crecimiento de fibroblastos en la acondroplasia y la hipocondroplasia en la población española.

BACKGROUND: Achondroplasia, the most common type of genetic dwarfism characterised by disproportionate short stature and other skeletal anomalies, results from a defect in the maturation of the chondrocytes in the growth plate cartilage. Hypochondroplasia, considered allelic to achondroplasia is clinically and genetically heterogeneous. Recent studies have mapped the gene on chromosome 4p16.3, and frequent mutations in the fibroblast growth factor 3 (FGFR3) have been described in these diseases in other populations. PATIENTS AND METHODS: Analysis of the FGFR3 gene mutations Gly380Arg and Asn540Lys in 20 Spanish patients (10 achondroplasic, 6 hypochondroplasic and 4 with skeletal dysplasias with some phenotypic and radiological characteristics of hypochondroplasia) by PCR and restriction analysis. RESULTS: All the achondroplasic patients have shown the same mutation (Gly380Arg) in the transmembrane domain of the receptor. Five hypochondroplasic patients presented the mutation Asn540Lys in the proximal thirosine kinase domain. CONCLUSIONS: Achondroplasia in this sample from Spanish patients is also homogeneous in its molecular basis. Genetic heterogeneity has been found in hypochondroplasia corresponding with the phenotypic diversity in this disease. Molecular analysis of FGFR3 may be an additional diagnostic tool and facilitates genetic counselling in these chondrodysplasias.