Incidentaloma adrenal: estudio descriptivo de una serie

El incidentaloma adrenal es aquella masa suprarrenal hallada casualmente al realizar una prueba de imagen por otro motivo. El estudio debe determinar su benignidad y funcionalidad. La controversia radica en el seguimiento. Se presenta un estudio de 67 pacientes con indicentaloma adrenal recogido en 5 años, estudio inicial y seguimiento a largo plazo. Se halló un 74,6% adenomas no funcionantes, 7,4% mielolipomas, 4,5% Síndrome de Cushing, 2,9% Hiperaldosteronismo primario, 1,5% feocromocitoma y metástasis. El seguimiento a largo plazo se realizó a los 6 y 18-24 meses, sin cambios. El estuido realizado apoya las guías actuales.

Morbiditat postoperatòria en pacients intervinguts d’un adenoma hipofisari: comparació dels tumors no funcionants i dels secretors d’hormona de creixement i corticotropa

La neurocirurgia és el tractament definitiu més utilitzat pels tumors hipofisaris. Objectiu: valorar les complicacions postquirúrgiques immediates(1º mes) i durant el 1º any dels adenomes hipofisaris secretors de GH, ACTH i no funcionants(NF) operats des del 2001. Metodologia: estudi observacional restrospectiu de 94 pacients (39H, 55D) amb edat a la cirurgia de 46,9±15,5 anys, intervinguts pels 2 mateixos neurocirurgians. Resultats: 40 pacients tenen alguna complicació immediata(42,5% dels NF, 37% GH i 48,5% ACTH) sense diferències en la freqüència de complicacions entre els 3 grups. Les complicacions més freqüents són: diabetis insípida transitòria(23,4%), fístula LCR(6,7%), sinusitis i meningitis(2,2%). Els secretors d'ACTH tenen una tendència a tenir més DI transitòria i sinusitis respecte els NF(p=0,071), mentre que els NF tendeixen a presentar més fístules LCR, meningitis i convulsions(p=0,08). En els GH, existeix major incidència de fístules LCR comparat amb els ACTH(p&0,05), sense diferències amb els NF. 10 pacients tenen complicacions al 1º any postquirúrgic(7,5% dels NF, 11,1% GH i 14,8% ACTH), destacant major incidència d'artromiàlgies i síndrome del túnel carpià en els ACTH comparat amb els altres 2 grups (p&0,05). Les variables més importants quan fem una predicció d'aparició de complicacions són: tipus de cirurgia utilitzada (més a craniotomies que als abordatges transesfenoidals) i presència d'extensió extraselar tumoral, sense ser significatiu(p=0,091). Conclusions: malgrat que els tumors d'ACTH són majoritàriament microdenomes(77,7%), i es presenten en pacients més joves, tendeixen a associar-se a major nombre de complicacions immediates i durant el primer any en comparació amb els NF i GH(97,5%, 81,4% macroadenomes respectivament).

Avaluació de la seguretat en els pacients diabètics

L’objectiu es analitzar l’efecte d’una intervenció educativa realitzada a professionals de la salut i sobre la seguretat dels pacients diabètics. Estudi d’intervenció aleatoritzat per conglomerats (5 ABS intervenció i 5 control). Valorem pacients de 45 a 75 anys diagnosticats de Diabetis Mellitus tipus 1 o 2. Realitzem una intervenció educativa estandaritzada als professionals, els avaluem mitjançant el test DAS-3 (Diabetes Attitude Scale); dels pacients valorem ítems relacionats amb el control de la malaltia. Analitzem l’efecte de la intervenció sobre les actituds i motivacions dels professionals i l’efecte sobre el grau de control de la malaltia en els pacients.

Eficacia analgésica de la infusión continua de anestésico local a nivel subfascial en cesárea: comparación de dos anestésicos locales

El dolor es una complicación frecuente tras cesárea. Últimamente, se está desarrollando una nueva técnica analgésica que consiste en la infiltración de anestésico local (AL) a nivel subfascial en la herida quirúrgica. Nuestro objetivo es comparar la eficacia analgésica de dos AL. Para ello evaluamos el grado de dolor, parámetros hemodinámicos, satisfacción de las pacientes y necesidad de analgesia de rescate. El análisis estadístico concluyó que no existían diferencias entre los dos tratamientos, con buen control del dolor, sin existir alteraciones hemodinámicas. Parece que la infiltración de un AL es eficaz en la reducción del dolor postoperatorio, con menor consumo de analgesia intravenosa, y sin aumento de efectos secundarios.

Funció gonadal en pacients obesos abans i després de cirurgia bariàtrica

Estudio observacional en 33 hombres obesos mórbidos sometidos a cirugía bariátrica con objetivo de analizar cambios del perfil gonadal tras pérdida de peso. La prevalencia de hipogonadismo basal (TT & 300 ng/dL y TL & 65 ng/dL) era 78,8% y 51,5%; y un año tras cirugía 6% y 15%. Al año de la cirugía se observó incremento de TT, TL, SHBG y FSH y disminución de estradiol y prolactina. La edad y PPP se asociaban significativa e independientemente al porcentaje de cambio de TT. El hipogonadismo asociado a hombres con obesidad mórbida es muy prevalente y reversible con pérdida ponderal.

To select or to weigh: a comparative study of linear combination schemes for superparent-one-dependence estimators

We conduct a large-scale comparative study on linearly combining superparent-one-dependence estimators (SPODEs), a popular family of seminaive Bayesian classifiers. Altogether, 16 model selection and weighing schemes, 58 benchmark data sets, and various statistical tests are employed. This paper's main contributions are threefold. First, it formally presents each scheme's definition, rationale, and time complexity and hence can serve as a comprehensive reference for researchers interested in ensemble learning. Second, it offers bias-variance analysis for each scheme's classification error performance. Third, it identifies effective schemes that meet various needs in practice. This leads to accurate and fast classification algorithms which have an immediate and significant impact on real-world applications. Another important feature of our study is using a variety of statistical tests to evaluate multiple learning methods across multiple data sets.

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.

Allosteric conversation in the androgen receptor ligand-binding domain surfaces

Androgen receptor (AR) is a major therapeutic target that plays pivotal roles in prostate cancer (PCa) and androgen insensitivity syndromes. We previously proposed that compounds recruited to ligand-binding domain (LBD) surfaces could regulate AR activity in hormone-refractory PCa and discovered several surface modulators of AR function. Surprisingly, the most effective compounds bound preferentially to a surface of unknown function [binding function 3 (BF-3)] instead of the coactivator-binding site [activation function 2 (AF-2)]. Different BF-3 mutations have been identified in PCa or androgen insensitivity syndrome patients, and they can strongly affect AR activity. Further, comparison of AR x-ray structures with and without bound ligands at BF-3 and AF-2 showed structural coupling between both pockets. Here, we combine experimental evidence and molecular dynamic simulations to investigate whether BF-3 mutations affect AR LBD function and dynamics possibly via allosteric conversation between surface sites. Our data indicate that AF-2 conformation is indeed closely coupled to BF-3 and provide mechanistic proof of their structural interconnection. BF-3 mutations may function as allosteric elicitors, probably shifting the AR LBD conformational ensemble toward conformations that alter AF-2 propensity to reorganize into subpockets that accommodate N-terminal domain and coactivator peptides. The induced conformation may result in either increased or decreased AR activity. Activating BF-3 mutations also favor the formation of another pocket (BF-4) in the vicinity of AF-2 and BF-3, which we also previously identified as a hot spot for a small compound. We discuss the possibility that BF-3 may be a protein-docking site that binds to the N-terminal domain and corepressors. AR surface sites are attractive pharmacological targets to develop allosteric modulators that might be alternative lead compounds for drug design.

Comission 49: Interplanetary plasma and heliosphere. TRIENNIAL REPORT 2006 - 2009

Commission 49 covers research on the solar wind, shocks and particle acceleration, both transient and steady-state, e.g., corotating, structures within the heliosphere, and the termination shock and boundary of the heliosphere. The present triennal report is particularly rich in important results and events. The crossing of the solar wind termination shock by Voyager 2 in 2007 is a highlight and a milestone that will certainly have important consequences for astrophysical processes in general (Section 7). The fiftieth anniversary of the International Geophysical Year (19571958), which is also the fiftieth anniversary of the birth of the Space Age, was marked not only by celebrations and a strong Education and Public Outreach Program, but also by efforts in coordinating present observations and in starting new scientific programs, particularly implying developing countries (Section 8). Studies of solar energetic particles (Section 3) and the related radio bursts (Section 4) benefited from new data from a number of spacecraft. The STEREO mission was launched in October 2006 and has obtained new results on 3-D aspects of the inner heliosphere. Meanwhile, solar cycle 24 is expected to become active soon, following what is already the deepest solar minimum of the space age...