13Check_RNA: a tool to evaluate 13C chemical shift assignments of RNA.

Motivation: Chemical shifts (CS) are an important source of structural information of macromolecules such as RNA. In addition to the scarce availability of CS for RNA, the observed values are prone to errors due to a wrong re-calibration or miss assignments. Different groups have dedicated their efforts to correct CS systematic errors on RNA. Despite this, there are not automated and freely available algorithms for evaluating the referencing of RNA 13 C CS before their deposition to the BMRB or re-reference already deposited CS with systematic errors. Results: Based on an existent method we have implemented an open source python module to correct 13 C CS (from here on 13Cexp) systematic errors of RNAs and then return the results in 3 formats including the nmrstar one. Availability and implementation: This software is available on GitHub at https://github.com/BIOS-IMASL/13Check_RNA under a MIT license. Supplementary information: Supplementary data are available at Bioinformatics online.

Finite Dimension: A Mathematical Tool to Analise Glycans.

There is a need to develop widely applicable tools to understand glycan organization, diversity and structure. We present a graph-theoretical study of a large sample of glycans in terms of finite dimension, a new metric which is an adaptation to finite sets of the classical Hausdorff "fractal" dimension. Every glycan in the sample is encoded, via finite dimension, as a point of Glycan Space, a new notion introduced in this paper. Two major outcomes were found: (a) the existence of universal bounds that restrict the universe of possible glycans and show, for instance, that the graphs of glycans are a very special type of chemical graph, and (b) how Glycan Space is related to biological domains associated to the analysed glycans. In addition, we discuss briefly how this encoding may help to improve search in glycan databases.

Algorithm for early discharge after total thyroidectomy using PTH to predict hypocalcemia: prospective study.

PURPOSE: Hypocalcemia is the most common complication after total thyroidectomy. The aim of this study was to determine whether postoperative parathyroid hormone (PTH) levels predict hypocalcemia in order to design an algorithm for early discharge. METHODS: We present a prospective study including patients who underwent total thyroidectomy. Hypocalcemia was defined as serum ionized calcium < 1.09 mmol/L or clinical evidence of hypocalcemia. PTH measurement was performed preoperatively and at 1, 3, and 6 h postoperatively. The percent decline of preoperative values was calculated for each time point. RESULTS: One hundred and six patients were included. Thirty-six (33.9%) patients presented hypocalcemia. A 50% decline in PTH levels at 3 h postoperatively showed the highest sensitivity and specificity to predict hypocalcemia (91 and 73%, respectively). No patients with a decrease <35% developed hypocalcemia (100% sensitivity), and all patients with a decrease >80% had hypocalcemia (100% specificity). CONCLUSIONS: PTH determination at 3 h postoperatively is a reliable predictor of hypocalcemia. According to the proposed algorithm, patients with less than 80% drop in PTH levels can be safely discharged the day of the surgery.

Melanoma maligno gastrointestinal en paciente albino: a propósito de un caso / Gastrointestinal melanoma in an albino patient: Report of a case

Los albinos tienen predisposición al padecimiento de determinados tipos de cáncer cutáneo, pero el melanoma no es común. Entre los pocos artículos que documentan su aparición en estos pacientes, la afección gastrointestinal por melanoma aparece con relativa frecuencia, ya sea en forma de tumor primario o metástasis. Se presenta el caso de una paciente mujer de 70 años con una lesión gástrica y otra intestinal, detectadas mediante tomografía computada. El estudio anatomopatológico fue compatible con el diagnóstico de melanoma amelanótico. Pese a su escasa incidencia en albinos, el melanoma es una opción que no puede descartarse. Es importante, además, revisar los diferentes componentes del tracto gastrointestinal ante la existencia (o no) de un melanoma primario conocido...

Melanoma maligno gastrointestinal en paciente albino: a propósito de un caso

Los albinos tienen predisposición al padecimiento de determinados tipos de cáncer cutáneo, pero el melanoma no es común. Entre los pocos artículos que documentan su aparición en estos pacientes, la afección gastrointestinal por melanoma aparece con relativa frecuencia, ya sea en forma de tumor primario o metástasis. Se presenta el caso de una paciente mujer de 70 años con una lesión gástrica y otra intestinal, detectadas mediante tomografía computada. El estudio anatomopatológico fue compatible con el diagnóstico de melanoma amelanótico. Pese a su escasa incidencia en albinos, el melanoma es una opción que no puede descartarse. Es importante, además, revisar los diferentes componentes del tracto gastrointestinal ante la existencia (o no) de un melanoma primario conocido.(AU)

Albinos are predisposed to suffer certain types of skin cancer, but not usually melanoma, with just a few reports documenting it .Gastrointestinal tract is a relatively frequent site of melanoma occurrence, weather as a primary tumour or metastasis. We report a case of a 70 year-old female patient who underwent a computed tomography where a gastric and a bowel tumor were found. The pathology study was compatible with the diagnosis of an amelanotic melanoma. Despite that the diagnosis of melanoma in albine patients is a rare finding, it must be considered. It is also important to search through the digestive system even if there is no primary melanoma known.(AU)

Improving reading comprehension: From metacognitive intervention on strategies to the intervention on working memory executive processes / Mejorando la comprensión lectora: Desde la intervención metacognitiva en estrategias a la intervención en los procesos ejecutivos de la memoria operativa

Many students may read fluently but have difficulties constructing meaning from texts. Difficulties with reading comprehension have many implications at school. In particular, problems understanding texts interfere with studying and learning from text. Reading comprehension has improved in the last 30 years focusing on intervention programs that work with strategies in which metacog-nition plays a crucial role. However, recent years have seen relevant advances in the study of the relationship between working memory (WM), particularly executive processes, and reading comprehension. In this paper, we present how the last 20 years of our research has evolved regarding metacognitive intervention from text comprehension strategies, as the main idea and summarization to the intervention on WM's executive processes during reading. Thus, our more recent empirical data has shown that text comprehension can be improved after specific training on the executive functions of working memory (e.g., focusing, switching, connecting and updating mental representations, and the inhibition of irrelevant information) in Primary school students.

Muchos estudiantes pueden leer de forma fluida pero presentan dificultades para construir significados a partir de los textos. Las dificultades de compresión lectora tienen varias implicaciones en la escuela. En particular, los problemas de comprensión de textos interfieren con el estudio y el aprendizaje desde el texto. La comprensión de lectura se ha mejorado en los últimos 30 años enfocándose en los programas de intervención que trabajan con estrategias en las cuales la metacognición juega un papel crucial. Sin embargo, en años recientes han sido relevantes los avances en el estudio de las relaciones entre la memoria de trabajo (WM), particularmente el proceso ejecutivo, y la comprensión de lectura. En este artículo presentamos la manera como se ha desarrollado nuestra investigación en los últimos 20 años, en relación con intervención metacognitiva desde las estrategias de comprensión de textos, tales como la idea principal y el resumen en la intervención sobre el proceso ejecutivo de WM durante la lectura. Así, nuestros datos empíricos recientes han mostrado que la comprensión de textos puede ser mejorada después del tratamiento específico sobre las funciones ejecutivas de memoria de trabajo (e.g., enfocándose, cambiando, conectando y actualizando las representaciones mentales y la inhibición de información irrelevante) en niños de escuela primaria.

Improvement in motor and cognitive impairment after hyperbaric oxygen therapy in a selected group of patients with cerebrovascular disease: a prospective single-blind controlled trial.

BACKGROUND: Clinical and experimental evidence suggests that a localized decrease in oxygen brain tissue availability contributes to the neurological deficit in patients with cerebrovascular disease (CVD) who also present with frontal leukoaraiosis (LA) (periventricular hypodensity on CT scan) and lacunar infarcts. In a prospective controlled trial blinded to patients but not to investigators, we tested the effect of HBO2 on this group of patients. METHODS: Selected patients with symptomatic CVD, LA and lacunar infarcts received daily exposures of 45 minutes for 10 days to hyperbaric oxygen (n=18, HBO2 group) or hyperbaric air (n=8, control group). The control group subsequently received HBO2. Scores of conventional scales for motor and cognitive functions were obtained and videotaped before and after exposure. After the exposures, participants were followed on a monthly basis with systematic clinical neurological examination for up to 6 months. Results. There was a statistically significant improvement in all scales for the HBO2 group compared with the placebo group and in the placebo group after receiving HBO2 (p<0.05). Neurological improvement persisted in the majority of patients for up to 6 months. Repetition of the HBO2 protocol in 9 patients in whom symptoms recurred after 6 months resulted in improvement of symptoms. CONCLUSIONS: These data provide evidence consistent with the notion that HBO2 improves neurological function in patients with CVD, lacunar infarcts and frontal LA. Because of the lack of investigator blinding and a relatively small sample size in this study, larger, randomized controlled studies are needed to further test this hypothesis and to further define the role of oxygen therapy for brain repair in chronic brain disease.

Wavelet transform analysis of heart rate variability during myocardial ischaemia.

Analysis of heart rate variability (HRV) is a valuable, non-invasive method for quantifying autonomic cardiac control in humans. Frequency-domain analysis of HRV involving myocardial ischaemic episodes should take into account its non-stationary behaviour. The wavelet transform is an alternative tool for the analysis of non-stationary signals. Fourteen patients have been analysed, ranging from 40 to 64 years old and selected from the European Electrocardiographic ST-T Database (ESDB). These records contain 33 ST episodes, according to the notation of the ESDB, with durations of between 40s and 12 min. A method for analysing HRV signals using the wavelet transform was applied to obtain a time-scale representation for very low-frequency (VLF), low-frequency (LF) and high-frequency (HF) bands using the orthogonal multiresolution pyramidal algorithm. The design and implementation using fast algorithms included a specially adapted decomposition quadrature mirror filter bank for the frequency bands of interest. Comparing a normality zone against the ischaemic episode in the same record, increases in LF (0.0112 +/- 0.0101 against 0.0175 +/- 0.0208 s2 Hz(-1); p<0.1) and HF (0.0011 +/- 0.0008 against 0.00 17 +/- 0.0020 s2 Hz(-1); p<0.05) were obtained. The possibility of using these indexes to develop an ischaemic-episode classifier was also tested. Results suggest that wavelet analysis provides useful information for the assessment of dynamic changes and patterns of HRV during myocardial ischaemia.

Complicaciones de la tiroidectomía total / Complications of total Thyroidectomy

La tiroidectoimía total es realizada con relativa frecuencia para el tratamiento tanto de patología maligna como en casos específicos de patología benigna de la glándula tiroides. La cifra de complicaciones varía en las distintas series publicadas. El objetivo de este trabajo es determinar las características y el porcentaje de complicaciones postoperatorias de la tiroidectomía total....La tiroidectomía total, realizada por cirujanos entrenados en la especialidad, es un procedimiento seguro y con una morbilidad aceptable

Complicaciones de la tiroidectomía total / Complications of total Thyroidectomy

La tiroidectoimía total es realizada con relativa frecuencia para el tratamiento tanto de patología maligna como en casos específicos de patología benigna de la glándula tiroides. La cifra de complicaciones varía en las distintas series publicadas. El objetivo de este trabajo es determinar las características y el porcentaje de complicaciones postoperatorias de la tiroidectomía total....La tiroidectomía total, realizada por cirujanos entrenados en la especialidad, es un procedimiento seguro y con una morbilidad aceptable

Influence of lysine content and pH on the stability of alanine-based copolypeptides.

To account for the relative contributions of lysine and alanine residues to the stability of alpha-helices of copolymers of these two residues, conformational energy calculations were carried out for several hexadecapeptides at several pHs. All the calculations considered explicitly the coupling between the conformation of the molecule and the ionization equilibria as a function of pH. The total free energy function used in these calculations included terms that account for the solvation free energy and free energy of ionization. These terms were evaluated by means of a fast multigrid boundary element method. Reasonable agreement with experimental values was obtained for the helix contents and vicinal coupling constants ((3)J(HNalpha)). The helix contents were found to depend strongly on the lysine content, in agreement with recent experimental results of Williams et al. (Journal of the American Chemical Society, 1998, Vol. 120, pp. 11033-11043) In the lowest energy conformation computed for a hexadecapeptide containing 3 lysine residues at pH 6, the lysine side chains are preferentially hydrated; this decreases the hydration of the backbone CO and NH groups, thereby forcing the latter to form hydrogen bonds with each other in the helical conformation. The lowest energy conformation computed for a hexadecapeptide containing 6 lysine residues at pH 6 shows a close proximity between the NH3(+) groups of the lysine side chains, a feature that was previously observed in calculations of short alanine-based oligopeptides. The calculation on a blocked 16-mer of alanine shows a 7% helix content based on the Boltzmann averaged vicinal coupling constants computed from the dihedral angles phi, consistent with previous experimental evidence on triblock copolymers containing a central block of alanines, and with earlier theoretical calculations.

Physical reasons for the unusual alpha-helix stabilization afforded by charged or neutral polar residues in alanine-rich peptides.

We have carried out conformational energy calculations on alanine-based copolymers with the sequence Ac-AAAAAXAAAA-NH(2) in water, where X stands for lysine or glutamine, to identify the underlying source of stability of alanine-based polypeptides containing charged or highly soluble polar residues in the absence of charge-charge interactions. The results indicate that ionizable or neutral polar residues introduced into the sequence to make them soluble sequester the water away from the CO and NH groups of the backbone, thereby enabling them to form internal hydrogen bonds. This solvation effect dictates the conformational preference and, hence, modifies the conformational propensity of alanine residues. Even though we carried out simulations for specific amino acid sequences, our results provide an understanding of some of the basic principles that govern the process of folding of these short sequences independently of the kind of residues introduced to make them soluble. In addition, we have investigated through simulations the effect of the bulk dielectric constant on the conformational preferences of these peptides. Extensive conformational Monte Carlo searches on terminally blocked 10-mer and 16-mer homopolymers of alanine in the absence of salt were carried out assuming values for the dielectric constant of the solvent epsilon of 80, 40, and 2. Our simulations show a clear tendency of these oligopeptides to augment the alpha-helix content as the bulk dielectric constant of the solvent is lowered. This behavior is due mainly to a loss of exposure of the CO and NH groups to the aqueous solvent. Experimental evidence indicates that the helical propensity of the amino acids in water shows a dramatic increase on addition of certain alcohols, such us trifluoroethanol. Our results provide a possible explanation of the mechanism by which alcohol/water mixtures affect the free energy of helical alanine oligopeptides relative to nonhelical ones.

Combination therapy with hydroxyurea versus without hydroxyurea as first line treatment options for antiretroviral-naive patients.

PURPOSE: This study analyzed whether combination therapy with hydroxyurea (HU) could be considered as first line treatment for antiretroviral-naive patients. METHOD: The prospective open-label study was carried out from March 1996 to May 2000. The antiretroviral treatments were treatment 1-didanosine 400 mg/day, stavudine 60/80 mg/day, and HU 500 mg/day; treatment 2-two nucleosides plus a protease inhibitor; treatment 3-didanosine, indinavir, and HU (500-1,000 mg/day). The viral load (VL) and CD4 determinations were performed at weeks 24, 48, 72, and 96. RESULTS: The sample comprised 284 patients. The distribution of patients by levels of VL and CD4 were similar in the three treatment groups. At week 24, patients receiving T1 and T3 achieved higher percentages of undetectable VL (89% and 81%, respectively) with no significant differences (p =.127) between them. The T2 group showed a lower proportion (58%) of undetectable VL, which was significantly lower than T1 (p <.0001) and T3 (p <.0007). At week 48, the results were similar to week 24. At week 96, nearly all patients had undetectable viral load (UVL). The analysis of adverse effects showed that the T2 group at week 48 had a greater proportion of adverse effects that was significantly different from T1 (p =.0026); T3 had intermediate values with no significant difference from T2 (p =.45) and from T1 (p =.048). At week 48, T1 showed higher adherence level with significant difference from the other two treatments. CONCLUSION: Patients were followed for some 96 weeks and, with an intention-to-treat analysis, were found to do better virologically and Clinically in treatment groups containing HU. The combination of antiretroviral drugs with HU may be an excellent option as initial therapy because of its strong antiretroviral action, its lower rate of adverse effect, and the smaller cost as compared to other regimens.

[Hyperbaric oxygenation in subcortical frontal syndrome due to small artery disorders with leukoaraiosis]. / Oxigenoterapia hiperbárica en el síndrome frontal subcortical por enfermedad de pequeñas arterias con leucoaraiosis.

INTRODUCTION: Frontal leukoaraiosis (LA) is a common finding in patients with subcortical small-vessel disease and currently its pathogenesis is attributed to ischemic-hypoxic mechanisms. It associates to a vascular subcortical frontal syndrome (VSFS) for which an effective treatment does not exist. CLINICAL CASES: We present four subjects from a prospective patient-blind controlled pilot trial to study efficacy and safety of hyperbaric oxygen therapy (HBO) vs hyperbaric air in VSFS with LA. All of them had frontal or extended LA on computed tomography scan and lacunes in basal ganglia and centrum ovale, with moderate to severe gait disorders, urinary dysfunction, cognitive impairment, and dependence in the daily living activities. Deficits had begun two to ten years before and had remained stable three months previous to the treatment. Patients were assessed with validated scales and tests one week before and after being administrated ten daily sessions of HBO at 2.5 atmospheres absolute for 45 minutes with a multiplace chamber. Serious adverse effects did not occur. After treatment a noticeable gait, urinary and cognitive improvement was observed in all subjects, increasing their independence. They remained clinically improved during four to five months, after which the previous deficits reappeared. Then, three patients received ten daily sessions of air at 1.1 atmospheres absolute for 45 minutes (controls) and the other a new HBO regimen, which improved as the first time. From the controls, there were no changes in two, while the other did only improve cognitively. CONCLUSION: These patients show that HBO is effective and safety in reversing, at least partially, although at great length, chronic neurological deficits associated to vascular frontal LA, highlighting that a functional reserve therapeutically useful exists.

Role of hydrophobicity and solvent-mediated charge-charge interactions in stabilizing alpha-helices.

A theoretical study to identify the conformational preferences of lysine-based oligopeptides has been carried out. The solvation free energy and free energy of ionization of the oligopeptides have been calculated by using a fast multigrid boundary element method that considers the coupling between the conformation of the molecule and the ionization equilibria explicitly, at a given pH value. It has been found experimentally that isolated alanine and lysine residues have somewhat small intrinsic helix-forming tendencies; however, results from these simulations indicate that conformations containing right-handed alpha-helical turns are energetically favorable at low values of pH for lysine-based oligopeptides. Also, unusual patterns of interactions among lysine side chains with large hydrophobic contacts and close proximity (5-6 A) between charged NH3+ groups are observed. Similar arrangements of charged groups have been seen for lysine and arginine residues in experimentally determined structures of proteins available from the Protein Data Bank. The lowest-free-energy conformation of the sequence Ac-(LYS)6-NMe from these simulations showed large pKalpha shifts for some of the NH3+ groups of the lysine residues. Such large effects are not observed in the lowest-energy conformations of oligopeptide sequences with two, three, or four lysine residues. Calculations on the sequence Ac-LYS-(ALA)4-LYS-NMe also reveal low-energy alpha-helical conformations with interactions of one of the LYS side chains with the helix backbone in an arrangement quite similar to the one described recently by (Proc. Natl. Acad. Sci. U.S.A. 93:4025-4029). The results of this study provide a sound basis with which to discuss the nature of the interactions, such as hydrophobicity, charge-charge interaction, and solvent polarization effects, that stabilize right-handed alpha-helical conformations.

Isolation of verotoxin-producing Escherichia coli O-rough:K1:H7 from two patients with traveler's diarrhea.

Two Escherichia coli O-rough:K1:H7 strains producing verotoxin 1 that were isolated from stool samples of two travelers with diarrhea who consulted our clinic after trips to the Indian Subcontinent and Central America were characterized. Both strains were sorbitol negative, the same phenotype presented by E. coli O157:H7, but in contrast they were beta-glucuronidase positive. Low-frequency restriction analysis of chromosomal DNA and pulsed-field gel electrophoresis and repetitive extragenic palindrome-PCR showed that both strains were epidemiologically related. The illness was self-limited in both cases but involved long-duration, watery diarrhea (10 to 50 days) accompanied by abdominal cramps and flatulence. This serotype should be taken into account as a possible cause of traveler's diarrhea.

Heart transplantation in Chagas' disease. 10 years after the initial experience.

BACKGROUND: Heart transplantation (HT) as a therapeutic option for end-stage chronic Chagas' heart disease (CCHD) is controversial. Reactivation of Trypanosoma cruzi infection and recurrence of the disease in the allograft are likely to occur. Furthermore, active myocarditis has been reported to predispose patients to an increased incidence and severity of rejection. METHODS AND RESULTS: We prospectively investigated the long-term follow-up of 10 patients with CCHD who underwent HT. Immunosuppression was based on cyclosporine A and azathioprine. T cruzi reactivation was prevented with benzonidazole. Besides allograft rejection surveillance, T cruzi infection was monitored through blood tests, myocardial biopsies, and serological tests. Over a mean follow-up period of 34 +/- 38 months (range, 73 to 124 months), 7 patients are alive and in NYHA functional class I. Life expectancy was 78% for the second year and 65% for 10 years. Rejection was less frequent in chagasic than in age- and sex-matched control patients (mean +/- SD, 1.60 +/- 1.26 versus 5.70 +/- 1.89 episodes per patient, respectively; P = .0001); decreased severity of rejection was also observed (P = .006). T cruzi parasitemias detected on three occasions were successfully treated with benzonidazole. There were no signs of recurrence of the disease in the allograft. CONCLUSIONS: These results suggest an important role of HT in the treatment of CCHD. There was a low frequency of T cruzi infection reactivation and no signs of recurrence of the disease in the allograft. The surprisingly decreased rejection incidence and severity require further studies for elucidation.