Multisession anodal epidural direct current stimulation of the auditory cortex delays the progression of presbycusis in the Wistar rat.

Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.

Reward and fictive prediction error signals in ventral striatum: asymmetry between factual and counterfactual processing.

Reward prediction error, the difference between the expected and obtained reward, is known to act as a reinforcement learning neural signal. In the current study, we propose a model fitting approach that combines behavioral and neural data to fit computational models of reinforcement learning. Briefly, we penalized subject-specific fitted parameters that moved away too far from the group median, except when that deviation led to an improvement in the model's fit to neural responses. By means of a probabilistic monetary learning task and fMRI, we compared our approach with standard model fitting methods. Q-learning outperformed actor-critic at both behavioral and neural level, although the inclusion of neuroimaging data into model fitting improved the fit of actor-critic models. We observed both action-value and state-value prediction error signals in the striatum, while standard model fitting approaches failed to capture state-value signals. Finally, left ventral striatum correlated with reward prediction error while right ventral striatum with fictive prediction error, suggesting a functional hemispheric asymmetry regarding prediction-error driven learning.

Cross-modal reaction of auditory and visual cortices after long-term bilateral hearing deprivation in the rat.

Visual cortex (VC) over-activation analysed by evoked responses has been demonstrated in congenital deafness and after long-term acquired hearing loss in humans. However, permanent hearing deprivation has not yet been explored in animal models. Thus, the present study aimed to examine functional and molecular changes underlying the visual and auditory cross-modal reaction. For such purpose, we analysed cortical visual evoked potentials (VEPs) and the gene expression (RT-qPCR) of a set of markers for neuronal activation (c-Fos) and activity-dependent homeostatic compensation (Arc/Arg3.1). To determine the state of excitation and inhibition, we performed RT-qPCR and quantitative immunocytochemistry for excitatory (receptor subunits GluA2/3) and inhibitory (GABAA-α1, GABAB-R2, GAD65/67 and parvalbumin-PV) markers. VC over-activation was demonstrated by a significant increase in VEPs wave N1 and by up-regulation of the activity-dependent early genes c-Fos and Arc/Arg3.1 (thus confirming, by RT-qPCR, our previously published immunocytochemical results). GluA2 gene and protein expression were significantly increased in the auditory cortex (AC), particularly in layers 2/3 pyramidal neurons, but inhibitory markers (GAD65/67 and PV-GABA interneurons) were also significantly upregulated in the AC, indicating a concurrent increase in inhibition. Therefore, after permanent hearing loss in the rat, the VC is not only over-activated but also potentially balanced by homeostatic regulation, while excitatory and inhibitory markers remain imbalanced in the AC, most likely resulting from changes in horizontal intermodal regulation.

Escala APACHE II para pacientes críticos con cáncer sólido. Estudio de reclasificación / APACHE II score for critically ill patients with a solid tumor: A reclassification study

Objetivo: Mejorar el rendimiento de la escala Acute Physiology and Chronic Health Evaluation (APACHE) II para la predicción de muerte hospitalaria en pacientes críticos con cáncer. Materiales y métodos: Estudio prospectivo de 522 pacientes con cáncer sólido admitidos en UCI. Se creó la «escala APACHE II para pacientes con cáncer sólido» (escala APACHE IIPCC); se adicionaron variables típicas del paciente oncológico crítico a la escala APACHE II general. Se evaluó la calibración (prueba de Hosmer-Lemeshow [H-L]) y discriminación (área bajo la curva de las características operativas del receptor [ACOR]). Se utilizó la mejora en la discriminación integrada (IDI), mejora neta en la reclasificación (NRI; 20% como valor de corte en el riesgo de muerte) y NRI cuantitativo (cNRI) para evaluar la mejora en la predicción de muerte hospitalaria con el nuevo modelo. Resultados: La mortalidad hospitalaria fue del 13%. La discriminación fue superior con la escala APACHE IICCP (ACOR = 0,91 [IC del 95% 0,87-0,94; p < 0,0001]) comparado con la escala APACHE II general (ACOR = 0,62 [IC del 95% 0,54-0,70; p = 0,002]). La calibración fue mejor con la escala APACHE IICCP (H-L p = 0,267 vs. p = 0,001). En el análisis de reclasificación se observó una mejora en la predicción de muerte con la escala APACHE IICCP (IDI = 0,2994 [p < 0,0001]; cNRI = 134,3% [IC del 95% 108,8-159,8%; p < 0,0001]; NRI = 41,5% [IC del 95% 23,7-59,3%; p < 0,0001]). Conclusiones: La escala APACHE IICCP fue superior a la escala APACHE II general en la predicción de muerte en pacientes críticos con cáncer sólido. Se requieren otros estudios que validen este nuevo modelo predictivo

Objective: To improve the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) II model for predicting hospital mortality in critically ill cancer patients. Materials and methods: This was a prospective cohort study of 522 patients admitted to ICU with a solid tumor. We developed the "APACHE II score for critically ill patients with a solid tumor" (APACHE IICCP score), in which typical variables of critically ill cancer patients were added to general APACHE II score. Calibration and discrimination were evaluated by Hosmer-Lemeshow test (H-L) and area under receiver operating characteristic curve (AROC), respectively. The improvement in predicting hospital mortality with the new model was assessed using a reclassification analysis by integrated discrimination improvement (IDI), net reclassification improvement (NRI; cut-off point of 20% in risk of death) and quantitative NRI (qNRI). Results: The hospital mortality rate was 13%. Discrimination was superior for APACHE IICCP score (AROC=0.91 [95% CI 0.87-0.94; P<.0001]) compared to general APACHE II score (AROC=0.62 [95% CI 0.54-0.70; P=.002]). Calibration was better using APACHE IICCP score (H-L; P=.267 vs. P=.001). In reclassification analysis, an improved mortality prediction was observed with APACHE IICCP score (IDI=0.2994 [P<.0001]; total qNRI=134.3% [95% CI 108.8-159.8%; P<.0001]; total NRI=41.5% [95% CI 23.7-59.3%; P<.0001]). Conclusions: The performance of APACHE IICCP score was superior to that observed for general APACHE II score in predicting mortality in critically ill patients with a solid tumor. Other studies validating this new predictive model are required

APACHE II score for critically ill patients with a solid tumor: A reclassification study. / Escala APACHE II para pacientes críticos con cáncer sólido. Estudio de reclasificación.

OBJECTIVE: To improve the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) II model for predicting hospital mortality in critically ill cancer patients. MATERIALS AND METHODS: This was a prospective cohort study of 522 patients admitted to ICU with a solid tumor. We developed the "APACHE II score for critically ill patients with a solid tumor" (APACHE IICCP score), in which typical variables of critically ill cancer patients were added to general APACHE II score. Calibration and discrimination were evaluated by Hosmer-Lemeshow test (H-L) and area under receiver operating characteristic curve (AROC), respectively. The improvement in predicting hospital mortality with the new model was assessed using a reclassification analysis by integrated discrimination improvement (IDI), net reclassification improvement (NRI; cut-off point of 20% in risk of death) and quantitative NRI (qNRI). RESULTS: The hospital mortality rate was 13%. Discrimination was superior for APACHE IICCP score (AROC=0.91 [95% CI 0.87-0.94; P<.0001]) compared to general APACHE II score (AROC=0.62 [95% CI 0.54-0.70; P=.002]). Calibration was better using APACHE IICCP score (H-L; P=.267 vs. P=.001). In reclassification analysis, an improved mortality prediction was observed with APACHE IICCP score (IDI=0.2994 [P<.0001]; total qNRI=134.3% [95% CI 108.8-159.8%; P<.0001]; total NRI=41.5% [95% CI 23.7-59.3%; P<.0001]). CONCLUSIONS: The performance of APACHE IICCP score was superior to that observed for general APACHE II score in predicting mortality in critically ill patients with a solid tumor. Other studies validating this new predictive model are required.

c-Fos and Arc/Arg3.1 expression in auditory and visual cortices after hearing loss: Evidence of sensory crossmodal reorganization in adult rats.

Cross-modal reorganization in the auditory and visual cortices has been reported after hearing and visual deficits mostly during the developmental period, possibly underlying sensory compensation mechanisms. However, there are very few data on the existence or nature and timeline of such reorganization events during sensory deficits in adulthood. In this study, we assessed long-term changes in activity-dependent immediate early genes c-Fos and Arc/Arg3.1 in auditory and neighboring visual cortical areas after bilateral deafness in young adult rats. Specifically, we analyzed qualitatively and quantitatively c-Fos and Arc/Arg3.1 immunoreactivity at 15 and 90 days after cochlea removal. We report extensive, global loss of c-Fos and Arc/Arg3.1 immunoreactive neurons in the auditory cortex 15 days after permanent auditory deprivation in adult rats, which is partly reversed 90 days after deafness. Simultaneously, the number and labeling intensity of c-Fos- and Arc/Arg3.1-immunoreactive neurons progressively increase in neighboring visual cortical areas from 2 weeks after deafness and these changes stabilize three months after inducing the cochlear lesion. These findings support plastic, compensatory, long-term changes in activity in the auditory and visual cortices after auditory deprivation in the adult rats. Further studies may clarify whether those changes result in perceptual potentiation of visual drives on auditory regions of the adult cortex.

Retrospective study assesing the role of MRI in the diagnostic procedures for early breast carcinoma: a correlation of new foci in the MRI with tumor pathological features

BACKGROUND: Use of breast magnetic resonance imaging (MRI) to detect breast cancer has generated significant debate. We analyze the role of breast MRI in the detection of additional disease and the need to perform additional biopsies in early breast carcinoma patients. In addition, we correlate the detection of new foci with tumor pathological features. METHODS: Early breast carcinoma patients that had undergone an MRI as well as a mammography as diagnostic procedures were included in the study. The following pathologic features were studied: carcinoma type, histological grade, estrogen receptors (ER), progesterone receptors (PR), HER2 and Ki67. Univariate analysis was conducted to ascertain significant correlation among detection of new foci and each of the tumor pathological features. RESULTS: Data from 98 patients have been analyzed: median age 49 years (range 35-79); carcinoma type: (a) infiltrative ductal carcinoma (n = 73, 74 %), (b) infiltrative lobular cancer (n = 12, 12 %), (c) ductal carcinoma in situ (n = 6, 6 %); amplified HER2 (n = 18, 18 %); grade III (n = 33, 33 %); Ki67 ≥ 25 % (n = 33, 33.67 %); positive ER and PR (n = 79, 80 %); triple negative tumors (n = 8, 8 %). MRI detected additional disease in 38 cases (39.58 %), and 20 led to an additional biopsy (20.4 %). Thirty-eight patients (39 %) underwent mastectomy. We found a statistically significant correlation between new foci in MRI and high Ki67 ≥ 25 % (p < 0.005). No other statistically significant correlation was established. CONCLUSION: MRI detected additional disease in 39 % cases, requiring an additional biopsy 20 %. Tumors with high proliferative index were significantly correlated with the detection of new foci in MRI (AU)

Retrospective study assessing the role of MRI in the diagnostic procedures for early breast carcinoma: a correlation of new foci in the MRI with tumor pathological features.

BACKGROUND: Use of breast magnetic resonance imaging (MRI) to detect breast cancer has generated significant debate. We analyze the role of breast MRI in the detection of additional disease and the need to perform additional biopsies in early breast carcinoma patients. In addition, we correlate the detection of new foci with tumor pathological features. METHODS: Early breast carcinoma patients that had undergone an MRI as well as a mammography as diagnostic procedures were included in the study. The following pathologic features were studied: carcinoma type, histological grade, estrogen receptors (ER), progesterone receptors (PR), HER2 and Ki67. Univariate analysis was conducted to ascertain significant correlation among detection of new foci and each of the tumor pathological features. RESULTS: Data from 98 patients have been analyzed: median age 49 years (range 35-79); carcinoma type: (a) infiltrative ductal carcinoma (n = 73, 74 %), (b) infiltrative lobular cancer (n = 12, 12 %), (c) ductal carcinoma in situ (n = 6, 6 %); amplified HER2 (n = 18, 18 %); grade III (n = 33, 33 %); Ki67 ≥ 25 % (n = 33, 33.67 %); positive ER and PR (n = 79, 80 %); triple negative tumors (n = 8, 8 %). MRI detected additional disease in 38 cases (39.58 %), and 20 led to an additional biopsy (20.4 %). Thirty-eight patients (39 %) underwent mastectomy. We found a statistically significant correlation between new foci in MRI and high Ki67 ≥ 25 % (p < 0.005). No other statistically significant correlation was established. CONCLUSION: MRI detected additional disease in 39 % cases, requiring an additional biopsy 20 %. Tumors with high proliferative index were significantly correlated with the detection of new foci in MRI.

Dislipemia del síndrome metabólico. Documento sumario del Foro HDL / Dyslipidemia of the metabolic syndrome. Summary document of the HDL-Forum

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Diagnóstico de síndrome metabólico. Adecuación de los criterios diagnósticos en nuestro medio. Recomendaciones del foro HDL. Resumen ejecutivo / Diagnosis of Metabolic Syndrome. Adaptation of Diagnostic Criteria in Our Setting. Recommendations of the Hdl Forum

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Breakthrough performance of stacks of dye-cellulosic fabric in affinity chromatography of lysozyme.

The breakthrough performance of stacks of dye-cellulosic fabric in affinity chromatography of lysozyme was investigated in batch and flow experiments. Breakthrough curves were significantly affected by flow rate and were not dependent on the feed solution concentration. System dispersion curves could not explain the flow-rate dependence. Breakthrough curves were analyzed by coupling the kinetic model for pore mass transfer as the only controlling resistance and a system dispersion model. From the analysis, pore film mass transfer resistance was found to be the leading rate-limiting factor when the residence time in the column is greater than 5 min. The model was used to predict the operating and design parameters needed to obtain sharp breakthrough curves. Selectivity studies using lysozyme and bovine serum albumin mixtures showed a high system selectivity for lysozyme.

Draw-fill batch culture mode for production of xylanases by Cellulomonas flavigena on sugar cane bagasse.

Draw-fill culture was evaluated as a method for xylanase production by Cellulomonas flavigena on sugar cane bagasse. Specific xylanase activity and volumetric xylanase activities were measured by harvesting 50%, 55%, 60% and 70% of fermented broth at the end of each subculture. Maximum specific (64 IU mg(-1) protein) and volumetric (166 IU ml(-1)) xylanase activities were obtained by harvesting 50-55% of broth. Values were 3.4 and 3.8 times greater than those obtained in batch cultures carried out under the same conditions. Enzyme productivity of 4.2 IU ml(-1) h(-1) was significantly greater than that obtained in continuous cultures (2.4 IU ml(-1) h(-1)) (P<0.05).

Osteoartropatía hipertrófica pnéumica / Hypertropic pneumic osteoarthropaty

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Biotransformation of n-hexadecane by cell suspension cultures of Cinchona robusta and Dioscorea composita.

This manuscript evaluates the phytotoxicity and biotransformation of n-hexadecane as well as peroxidase activity and cytochrome P450 concentration in microsomes for cell suspension cultures of Cinchona robusta and Dioscorea composita. Phytotoxicity was evaluated based on viability and growth. Cell cultures were exposed to a 2 and 4% (v/v) dose of n-hexadecane. The biotransformation of n-hexadecane was determined based on labeled recovery in polar, nonpolar, and cell residue fractions after cell culture extraction during exponential cell growth phase and stationary phase. Differences were observed in accumulation of label during cell growth phase and stationary phase for the cells of the two plants. Differences also were observed between phases for label in polar and nonpolar fractions. Thin-layer chromatography determined labeled intermediates and some were identified. The activity of peroxidase and concentration of cytochrome P450 was lower in C. robusta than in controls and greater in D. composita than in controls. In vitro biotransformation was not successful.

Rapid westernization of children's blood cholesterol in 3 countries: evidence for nutrient-gene interactions?

The aim of this study was to examine potential factors that modify blood cholesterol among children in countries in which dietary and lifestyle habits are becoming westernized. Population data on serum total and lipoprotein cholesterol, anthropometric indexes, and dietary intake were reviewed and compared for children aged 1-18 y from Japan, Spain, and the United States. The data show that total serum cholesterol in Japanese and Spanish children recently exceeded the 75th percentile for US children, primarily reflecting LDL cholesterol, although both LDL and HDL cholesterol contributed. Adiposity indexes do not explain the trends observed. Total and saturated fat intakes increased substantially in both Japan and Spain but in Japan are still lower than intakes in the United States. The Hegsted equation was used to relate differences in serum cholesterol to dietary fat intake. Changes in total serum cholesterol followed established dietary correlations among children in Spain, but not in Japan. Serum cholesterol in Japanese children was predicted to be 0.20-0.32 mmol/L lower than in US children; actual concentrations were considerably higher. These results suggest that a rapid westernization of children's blood cholesterol concentrations has occurred in Japan and Spain. Changes in fat intake predict changes in blood cholesterol in Spain, but not in Japan. Differences in genetic response to diet in certain populations, such as the Japanese, may explain higher blood cholesterol concentrations with lower fat intakes compared with the United States.

[Guidelines of the Spanish Society of Cardiology for cardiovascular disease prevention and cardiac rehabilitation]. / Guías de práctica clínica de la Sociedad Española de Cardiología en prevención cardiovascular y rehabilitación cardíaca.

The priorities for the prevention of cardiovascular diseases should be focused on patients with established disease and high risk subjects, with individual global risk always being taken into account. The current evidence on the influence of the main risk factors are unanimous (dyslipemia, tobacco, hypertension and diabetes mellitus), being somewhat less so in cases of sedentarism, obesity and the metabolic syndrome. The evidence concerning other risk factors still remains controversial. Guidelines for the control of the different risk factors should be based on the evidence derived from both epidemiological or clinical trials. The recommendations published by several scientific societies should also be followed. There are, at present, important evidence on the efficacy of smoking cessation, the treatment of arterial hypertension and particularly on the successful control of lipid levels with lipid-lowering drugs, especially with statins. There is also evidence on the need for rigorous control of diabetic patients not only in relation to the glucose levels but also to dyslipemia. The most efficient measures for a reduction in morbidity and mortality are cessation of smoking, appropriate hypertensive therapy, a comprehensive program of cardiac rehabilitation and overall the successful control of lipid levels with statins.

Síndrome de Cotard y neurosífilis / Cotard syndrome and neurosyphilis

Se presenta el caso de un paciente varón de 59 años de edad ingresado en la unidad de psiquiatría del Hospital General de Elche por presentar clínica consistente en mutismo, inhibición psicomotriz e ideas delirantes somáticas, de ruina y de perjuicio, que inicialmente fue diagnosticado de síndrome de Cotard y más tarde, después de realizar pruebas serológicas luéticas, de neurosífilis. En una primera valoración orgánica del paciente se omitió esta serología, lo que condujo a este error diagnóstico. Se comenta la importancia de solicitar de forma sistemática las pruebas serológicas luéticas ante trastornos mentales atípicos o con sintomatología abigarrada, cursen o no con manifestaciones neurológicas. Esto permitiría la instauración de tratamientos específicos con penicilina en los casos de neurosífilis que, como el presentado, responderían favorablemente. La mayor relevancia y prevalencia de la infección por el virus de la inmunodeficiencia humana sobre la infección sifilítica conducen al infradiagnóstico de la neurosífilis por la omisión de la serología pertinente por parte de los clínicos (AU)

The utility of < or =3-day-old whole-blood platelets in reducing the incidence of febrile nonhemolytic transfusion reactions.

BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTRs) to platelet transfusions have been linked to the presence of cytokines in supernatant plasma. Cytokine concentration is directly related to WBC content and storage time. This study evaluated the effect of limiting the storage time of random-donor platelet concentrates on the FNHTR rate. STUDY DESIGN AND METHODS: FNHTR rates were calculated retrospectively for single-donor apheresis platelet (SDP) and pooled random-donor platelet (PP) transfusions given during three consecutive 5-month study periods (November 1995 to February 1997) to patients on a single hematology/oncology/bone marrow transplant unit. Transfusion practice policies were: Baseline Period, SDPs preferred; Study Period A, PPs preferred; and Study Period B, < or =3-day-old PPs preferred. FNHTR rates were calculated from physicians' interpretations of reported reactions and the total number of SDP and PP transfusions in each period. SDPs were collected on two cell separators. All platelet components were filtered at issue in the laboratory by WBC-reduction filters. RESULTS: FNHTR rates for PP transfusions were: baseline, 11.1 percent (3/27); Study Period A, 4.6 percent (22/481); and Study Period B, 1.1 percent (3/282). The rates for SDP transfusions were 0. 15 percent (1/650), 0.75 percent (2/267), and 0.36 percent (1/273), respectively. The FNHTR rate for < or =3-day-old PPs was significantly less than the rate for older PPs (p = 0.0086 for Study Period A vs. Study Period B), and was not significantly different than that for SDPs (p = 0.33 for PPs vs. SDPs in Study Period B). CONCLUSION: Limiting transfusion of PPs to those stored