Quantitative chemoproteomic profiling reveals multiple target interactions of spongiolactone derivatives in leukemia cells.

The spongiolactones are marine natural products with an unusual rearranged spongiane skeleton and a fused ß-lactone ring. These compounds have potential anticancer properties but their mode of action has yet to be explored. Here we employ activity-based protein profiling to identify the targets of a more potent spongiolactone derivative in live cancer cells, and compare these to the targets of a simpler ß-lactone. These hits provide the first insights into the covalent mechanism of action of this natural product class.

Utilidad clínica del Antígeno Carcinoembrionario (ACE), Tomografía convencional (TC) y PET-CT en el diagnóstico de adenocarcinoma colorrectal recidivante / Clinical utility of Carcinoembryonic Antigen (ACE), conventional tomography (CT) and PET-CT in the diagnosis of recurrent colorectal adenocarcinoma

Introduction: Colorectal cancer is one of the most prevalent tumors in the world. In the surveillance setting of recurrent colorectal cancer, laboratory test like carncinoembryonic antigen (CEA) and imaging tests like computed tomography (CT) and positron emission tomography (PET/CT) are available. We performed this study to establish the predictive accuracy of these tests to an early identification of recurrent colorectal cáncer. Materials and Methods: Thirty six patients at stages I , III and IV, after single metastasis resection of colorectal cáncer were identified. We assessed the utility of CEA, CT and PET-CT in the follow-up of these patients to improve the diagnosis of recurrent disease. Results: Of 36 studied patients, 27 /75%) had recurrence; the median age was 61 year-old and the median lap-time 16 months. The PET PET/CT scan obtained the following results: sensitivity 96.7%, specificity 88.9%, positive predictive value 96.3%, negative predictive value 88.9%, positive likekihood ratio 8.7 and negative likelihood ratio 0.04. Discusion: The best tool to make diagnosis of colorectal cancer and its recurrence is PET­CT, however, none of these tests could make the diagnosis by themselves. It has to be confirmed by histopathologic studies plus other exams.

Comorbilidades y alteración de la calidad de vida en pacientes adultos con temblor esencial / Comorbidities and altered quality of life in adult patients with essential tremor

Introducción: El temblor esencial constituye el trastorno de movimiento más frecuente, se caracteriza por un temblor cinético postural de 4-12 Hz de frecuencia. Es una enfermedad crónica, progresiva y neurodegenerativa que tiene una repercusión heterogénea sobre la calidad de vida. Materiales y métodos: Se analizó la presencia de comorbilidades aplicando el índice de Charlson corregido, se valoró la correlación de estas patologías sobre la calidad de vida, ámbito emocional y funcionalidad de pacientes con temblor esencial. Resultados: Se estudiaron 132 pacientes con temblor esencial y no se encontró una correlación significativa entre la presencia de ansiedad, depresión y el estado cognitivo con la calidad de vida de éstos pacientes. Discusión: Las comorbilidades, medidas con el índice de Charlson, no se correlacionan con la calidad de vida y sus distintas esferas en pacientes con temblor esencial.

Introduction: Essential tremor is the most frequent movement disorder, is characterized as a postural tremor of 4-12 Hz frequency. Is a chronic, progressive and neurodegenerative disease that has a heterogeneous impact on quality of life, considering that it is a prevalent disease in older adults who have comorbidities aging, it is necessary to determine to what extent these comorbidities affect different areas of quality of life. Methods: The presence of comorbidities were analyzed using the Charlson index adjusted for age, focused on the relation of these comorbidities with the quality of life, emotional scope and functionality of patients with essential tremor. Results: One hundred and thirty two patientes with essential tremor were studied. We did not find a significant correlation between the presence of anxiety, depression and cognitive status with the quality of life of these patients. Discusion: Comorbidities assessed by the Charlson index do not correlate with quality of life in patients with essential tremor.

Blind colour separation of H&E stained histological images by linearly transforming the colour space.

Blind source separation methods aim to split information into the original sources. In histology, each dye component attempts to specifically characterize different microscopic structures. In the case of the hematoxylin-eosin stain, universally used for routine examination, quantitative analysis may often require the inspection of different morphological signatures related mainly to nuclei patterns, but also to stroma distribution. Stain separation is usually a preprocessing operation that is transversal to different applications. This paper presents a novel colour separation method that finds the hematoxylin and eosin clusters by projecting the whole (r,g,b) space to a folded surface connecting the distributions of a series of [(r-b),g] planes that divide the cloud of H&E tones. The proposed method produces density maps closer to those obtained with the colour mixing matrices set by an expert, when comparing with the density maps obtained using nonnegative matrix factorization (NMF), independent component analysis (ICA) and a state-of-the-art method. The method has outperformed three baseline methods, NMF, Macenko and ICA, in about 8%, 12% and 52% for the eosin component, whereas this was about 4%, 8% and 26% for the hematoxylin component.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry as an alternative to 16S rRNA gene sequencing for identification of difficult-to-identify bacterial strains.

Conventional methods are sometimes insufficient to identify human bacterial pathogens, and alternative techniques, often molecular, are required. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified with a valid score 45.9% of 410 clinical isolates from 207 different difficult-to-identify species having required 16S rRNA gene sequencing. MALDI-TOF MS might represent an alternative to 16S rRNA gene sequencing.

Improved COBAS TaqMan hepatitis C virus test (Version 2.0) for use with the High Pure system: enhanced genotype inclusivity and performance characteristics in a multisite study.

We have evaluated the COBAS TaqMan hepatitis C virus (HCV) test (version 2.0) for use with the High Pure system (HCVHPS V2), a new, revised real-time reverse transcription-PCR assay developed to improve the genotype quantitation of version 1.0 (HCVHPS V1). Revisions were made in the wash buffer and in the reverse transcription temperature. The genotype inclusivity of HCVHPS V2 was evaluated at three different sites, using HCVHPS V2, HCVHPS V1, and the COBAS AMPLICOR HCV MONITOR test (version 2.0) (CAHCM). The fully automated COBAS Ampliprep/COBAS TaqMan HCV test was also used in one of the participating laboratories. The mean differences in HCV RNA values between HCVHPS V2 and CAHCM and between HCVHPS V2 and HCVHPS V1 ranged from -0.21 to 0.13 log and from 0.24 to 1.27 log, respectively, with >0.5-log differences for genotypes 2, 3, 4, and 5. With a NIBSC panel of HCV genotypes 1 through 6, the measured HCVHPS V2 values were within 0.25 log of the nominal values for all 6 genotypes. When serial dilutions of genotype-specific clinical HCV specimens were tested, the assay showed a limit of detection between 10 and 20 IU/ml and a linear range of 25 IU/ml to 3.91 x 10(8) IU/ml. Clinical and analytical specificities of 100% were demonstrated with 100 HCV-seronegative specimens as well as with 12 non-HCV members of Flaviviridae and 22 additional microorganisms. These data indicate that HCVHPS V2 is a robust and accurate test for the quantitation of all six HCV genotypes and useful in monitoring viral load in all clinical HCV specimens.

Validating a computerized neuropsychological test battery for mixed ethnic lupus patients.

Patients with systemic lupus erythematosus (SLE) often show cognitive impairment on traditional neuropsychological tests; however, many of these tests are unsuitable for use with mixed ethnic populations. Computer-administered cognitive tests are promising, but have not been validated against traditional tests or with predominantly Hispanic samples. We gave 67 lupus patients a computer-administered test battery (Automated Neuropsychological Assessment Metrics--ANAM) and a battery of traditional neuropsychological tests. The two batteries were compared using correlation and multiple regression analyses. All patients were fluent in English, 54% were Hispanic and 13% were bilingual. Non-Hispanic patients were predominantly European American (37%). About 80% of patients were rated as impaired on traditional tests. Hispanics were younger, had less education and more current SLE disease activity than non-Hispanics; but did not differ in lifetime SLE-related organ damage or current steroid use. Hispanics and younger patients were more impaired on many of the traditional tests, while ANAM was not affected by Hispanic ethnicity or education. ANAM tests were moderately correlated with analogous traditional tests. Age and selected ANAM scores accounted for about 60% of the variance in the traditional battery. These results replicate the high prevalence of cognitive deficits in SLE found by others and suggest that computer-administered tests like ANAM may be useful for assessment of cognitive impairment in mixed-ethnic samples. Confounding variables such as age, education, English language fluency and prior experience with tests were identified and need to be controlled statistically or with comparison groups in future studies.

Respuesta sísmica de puentes chilenos con apoyos aislantes

La mayoría de los puentes importantes construidos en los últimos años y la vía elevada del metro de Santiago incluyen algún tipo de aislación sísmica y en varios de ellos se han instalado redes locales de acelerómetros con el fin de monitorear su respuesta frente a terremotos. En este trabajo se analizan los registros, tanto de vibraciones ambientales como de sismos, obtenidos a la fecha en el puente Marga-Marga de Viña del Mar, en el tramo elevado de la Línea 5 del metro de Santiago y en el puente Amolanas, ubicado en el kilómetro 308 de la carretera Panamericana Norte. Además, se presentan modelos de elementos finitos que reproducen las características dinámicas obtenidas experimentalmente.(AU)

Tumoración indolora en el brazo / Non-painful arm sweelling

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Neuropsychiatric syndromes in lupus: prevalence using standardized definitions.

OBJECTIVE: The San Antonio Lupus Study of Neuropsychiatric Disease is a longitudinal study designed to characterize the spectrum of and important risk factors for specific neuropsychiatric systemic lupus erythematosus (NPSLE) syndromes. METHODS: Subjects must meet criteria for SLE and must be at least 18 years of age. A standardized medical history, neurologic, rheumatologic, and psychiatric examinations, computerized neuropsychological evaluation, and serologic testing are performed. RESULTS: This report is based on the first 128 subjects (120 women and 8 men) who completed the initial study visit. Data from this initial study visit were evaluated for the prevalence of NPSLE using the American College of Rheumatology case definitions for 19 NPSLE syndromes. One or more NPSLE syndromes were present in 80% of subjects: cerebrovascular disease (2, 2%; ischemic stroke); headaches (73, 57%); mononeuropathy (9, 8%; median 8, ulnar 1); movement disorder (1, 1%; chorea); neuropathy, cranial (2, 2%; trigeminal); polyneuropathy (29, 22%; sensorimotor); seizures (21, 16%; partial); anxiety disorder (27, 24%); major depressive-like episode (37, 28%); mood disorder with depressive features (21, 19%); mood disorder with manic features (3, 3%); mood disorder with mixed features (1, 1%); psychosis (6, 5%). In a subset of 67 patients who received standardized neuropsychological testing, 21% had normal results. In the remainder, the following levels of impairment were seen: 43% mild, 30% moderate, and 6% severe. CONCLUSIONS: The prevalence of NPSLE was high in this cohort of unselected patients with SLE. Headaches, cognitive dysfunction, and psychiatric disorders were the most common NPSLE syndromes seen. These results will be easily comparable to other studies also using standardized diagnostic criteria. However, the lack of ethnicity and language-matched normative neuropsychological data may make comparisons of cognitive dysfunction in SLE populations difficult.

Enantioselective strategy to the spirocyclic core of Palau'amine and related bisguanidine marine alkaloids.

[structure: see text] An enantioselective strategy to the spirocyclic core found in the oroidin-derived family of bisguanidine marine alkaloids has been devised, premised on a biosynthetic proposal. Herein, we describe the successful implementation of this strategy, which entails a Diels-Alder reaction and a chlorination/ring contraction sequence that delivers the fully functionalized spirocyclic core. In this initial report, an intermolecular chlorination delivers a cyclopentane that is epimeric at C17 relative to the palau'amines and epimeric at C11 relative to the axinellamines.

Studies toward gymnodimine: development of a single-pot Hua reaction for the synthesis of highly hindered cyclic imines.

[structure: see text]. In studies directed toward gymnodimine and related marine toxins, a single-pot variation of the Hua cyclic imine synthesis has been developed. The reaction involves generation of N-trimethylsilyl lactams in situ followed by alkyllithium addition leading directly to cyclic imines. Importantly, this reaction proceeds efficiently with highly hindered alpha,alpha-dialkyl lactams, provided 1,2-dimethoxyethane (DME) is used as solvent, leading to stable cyclic imines. Overall, this transformation allows a one-pot coupling of an alkyliodide and a lactam to give a cyclic imine.

The utilitarian core hypothesis: cases for testing the stability of languages in the wake of conquest.

Based on the "utilitarian core hypothesis" that the most common words of a language develop early and resist change, the current exploratory study examined three test cases to suggest what happens to the common core of a language when its speakers are conquered. Whissell (1998) raised this issue by implication through demonstrating that the common core of English is largely Anglo-Saxon and thus survived the Norman Conquest. The notion that unique merits of English accounted for its success has a long history dating at least to Verstegan (1605/1976). We suggested that there are also instances of conquest in history illustrating the persistence of other languages despite the political subjugation of their speakers. Test cases included, in addition to the Norman Conquest of England, the Arab-Berber Conquest of most of the Iberian Peninsula, and Russian domination of modern Uzbekistan. The combined results suggest that persistence of a utilitarian core despite conquest is not an isolated instance. As a phenomenon it offers a more parsimonious account than do appeals to the special merits of English, Spanish, or Modern Uzbek. We have integrated these findings within a psychological framework pertaining to language use and change.

Studies toward (-)-gymnodimine: concise routes to the spirocyclic and tetrahydrofuran moieties.

[formula: see text] (-)-Gymnodimine is a member of a unique class of potent marine toxins possessing imines within a spirocylic array. Herein we report the synthesis of the tetrahydrofuran fragment and a strategy toward the spirocyclic imine fragment of this family of toxins. Key reactions include an asymmetric anti-aldol reaction to set the stereochemistry of the tetrahydrofuran and a formal, intermolecular Diels-Alder reaction involving an alpha-methylene-delta-lactam and a dienyne.

Synthesis and inhibitory action on HMG-CoA synthase of racemic and optically active oxetan-2-ones (beta-lactones).

A homologous series of both C3-unsubstituted and C3-methyl substituted oxetan-2-ones (beta-lactones) was investigated as potential inhibitors of yeast 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase. Several reported methods for racemic beta-lactone synthesis were studied for preparation of the target series. In addition, a novel aluminum-based Lewis acid obtained by combination of Et2AlCl with (1R,2R)-2-[(diphenyl)hydroxymethyl] cyclohexan-1-ol was studied for the asymmetric [2 + 2] cycloaddition of aldehydes and trimethylsilylketene. This Lewis acid exhibited good reactivity but variable enantioselectivity (22-85% ee). In in vitro assays using both native and recombinant HMG-CoA synthase from Saccharomyces cerevisiae, oxetan-2-ones mono-substituted at C4 with linear alkyl chains gave IC50s that decreased monotonically with chain length up to 10 carbons and then rose rapidly for longer chains. The trans isomers of 3-methyl-4-alkyl-oxetan-2-ones showed a similar trend but had 1.3- to 5.6-fold lower IC50s. The results imply a substantial hydrophobic pocket in this enzyme that interacts with both C-3 and C-4 substituents of oxetan-2-one inhibitors.