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BACKGROUND: Gated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population. METHODS: This is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab. RESULTS: 276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland-Altman plots demonstrated good agreement. CONCLUSIONS: The presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.

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ABSTRACT Epilepsy is the most common neurological pathology. Despite treatments available to patients, only 58% to 73% will be free of seizures. This uncertainty in treatment outcomes can lead to other psychiatric affectations in cases where treatment success may be in doubt. Seizure prediction models (SPMs) emerged as a measure to help determine when patients may be susceptible to an imminent crisis. These models are based on the continuous monitoring of patient's EEG signals and subsequent continuous analysis to identify features that differentiate ictal from interictal states. This is an ongoing field of research whose aim is to establish a robust set of features to feed the SPM and obtain a high degree of certainty regarding when the next seizure will occur. In this work we propose the analysis of phase differences of EEG as a method to extract features capable of discriminating ictal and preictal states in patients; specifically, the numeric distance between Q1 and Q3 of the distribution of phase differences. We compared this values to other phase synchronization methods and tested our hypothesis getting a p < 0.0009 with our proposed method.

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BACKGROUND: Placing the left ventricular (LV) lead in a viable segment with the latest mechanical activation (vSOLA) may be associated with optimal cardiac resynchronization therapy (CRT) response. We assessed the role of gated SPECT myocardial perfusion imaging (gSPECT MPI) in predicting clinical outcomes at 6 months in patients submitted to CRT. METHODS: Ten centers from 8 countries enrolled 195 consecutive patients. All underwent gSPECT MPI before and 6 months after CRT. The procedure was performed as per current guidelines, the operators being unaware of gSPECT MPI results. Regional LV dyssynchrony (Phase SD) and vSOLA were automatically determined using a 17 segment model. The lead was considered on-target if placed in vSOLA. The primary outcome was improvement in ≥1 of the following: ≥1 NYHA class, left ventricular ejection fraction (LVEF) by ≥5%, reduction in end-systolic volume by ≥15%, and ≥5 points in Minnesota Living With Heart Failure Questionnaire (MLHFQ). RESULTS: Sixteen patients died before the follow-up gSPECT MPI. The primary outcome occurred in 152 out of 179 (84.9%) cases. Mean change in LV phase standard deviation (PSD) at 6 months was 10.5°. Baseline dyssynchrony was not associated with the primary outcome. However, change in LV PSD from baseline was associated with the primary outcome (OR 1.04, 95% CI 1.01-1.07, P = .007). Change in LV PSD had an AUC of 0.78 (0.66-0.90) for the primary outcome. Improvement in LV PSD of 4° resulted in the highest positive likelihood ratio of 7.4 for a favorable outcome. In 23% of the patients, the CRT lead was placed in the vSOLA, and in 42% in either this segment or in a segment within 10° of it. On-target lead placement was not significantly associated with the primary outcome (OR 1.53, 95% CI 0.71-3.28). CONCLUSION: LV dyssynchrony improvement by gSPECT MPI, but not on-target lead placement, predicts clinical outcomes in patients undergoing CRT.

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PURPOSE: To analyze the evolution post-cardiac resynchronization therapy (CRT) in left ventricular non-compaction (LVNC) cardiomyopathy (CM) patients compared to other types of CM, according to clinical and functional variables, by using gated-SPECT myocardial perfusion imaging (MPI). METHODS: Ninety-three patients (60 ± 11 years, 28% women) referred for pre-CRT assessment were studied and divided into three groups: 1 (non-ischemic CM with LVNC, 11 patients), 2 (ischemic CM, 28 patients), and 3 (non-ischemic CM, 53 patients). All were studied by a 99mTc-MIBI gated-SPECT MPI at rest pre-CRT implantation and 6 ± 1 months after, including intraventricular dyssynchrony assessment by phase analysis. Quality of life was measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS: No differences in sex, atherosclerotic risk factors other than smoking habit, and MLHFQ results were found among groups. LVNC CM patients were younger, with greater QRS width and lower left ventricular ejection fraction (LVEF) at baseline, but the differences were not significant. No significant differences were found at baseline regarding ventricular function, although end-systolic volume was slightly higher in LVNC CM patients. Mean SRS was significantly higher (p < 0.0001) in ischemic patients (14.9) versus non-ischemic ones (8.7 in group 1 and 9 in group 2). At baseline, LVNC CM patients were significantly more dyssynchronous: Their phase standard deviation (PSD) was higher (89.5° ± 14.2°) versus groups 2 (65.2° ± 23.3°) and 3 (69.7° ± 21.7°), p = 0.007. Although the quality of life significantly improved in all groups, non-ischemic patients (with or without LVNC) showed a higher LVEF increase and volumes reduction at 6 months post-CRT. Dyssynchrony reduced post-CRT in all groups. Nevertheless, those more dyssynchronous at baseline (LVNC CM) exhibited the most significant intraventricular synchronism improvement: PSD was reduced from 89.5° ± 14.2° at baseline to 63.7° ± 20.5° post-CRT (p = 0.028). Six months post-CRT, 89% of patients were responders: 11 (100%) of those with LVNC CM, 25 (86%) of those with ischemic CM, and 47 (89%) of patients with non-ischemic CM. No patient with LVNC CM had adverse events during the follow-up. CONCLUSION: CRT contributes to a marked improvement in non-ischemic CM patients with non-compaction myocardium. Phase analysis in gated-SPECT MPI is a valuable tool to assess the response to CRT.

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INTRODUCTION: Left ventricular dyssynchrony (LVD) quantified by gated myocardial perfusion studies (MPS), through phase analysis (PA), has shown controversial results in myocardial stunning. OBJECTIVES: Assessment of LVD and regional wall motion abnormalities (RWMA) in normal and ischemic patients. METHODS: A cohort of 172 patients were studied. Summed Stress Score (SSS), Summed Resting Score (SRS), and Summed Difference Score (SDS) were evaluated. Group 1-patients with normal MPS (N = 133) and Group 2-patients with myocardial ischemia in the MPS (N = 39). LVD was evaluated through PA and RWM by visual analysis. RESULTS: SSS 0 vs 9.8 ± 3.9 P = .0001; SDS 0 vs 9.8 ± 3.9 P = .0001; SRS 0 vs 0 P = NS, in G1 and G2. Significant differences were found in LVD between G1 and G2, bandwidth 36 ± 14 vs 63 ± 46 P = .0001; standard deviation 16 ± 10 vs 26 ± 15 P = .0001. In G1, 16% had LVD vs RWMA in 0%, P = .0001 and in G2, 59% with LVD vs 33% with RWMA, P = .03. Sensitivity for LVD 59% and for RWMA 33%, P = .03 and specificity for LVD 83% and for RWMA 100%, P = .0001. CONCLUSION: Ischemic patients have LVD post-stress due to myocardial stunning. LVD measured by PA could be a useful tool to identify ischemia.

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Resumen Antecedentes: La enfermedad coronaria es una de las principales causas de morbimortalidad en los países occidentales. En etapas avanzadas de la enfermedad, los procesos de remodelación miocárdica pueden conducir a insuficiencia cardíaca progresiva y disfunción ventricular izquierda. El análisis de fase de los estudios de perfusión miocárdica Gated-SPECT muestra parámetros que han sido caracterizados como marcadores válidos de asincronía ventricular. Objetivo: Evaluar los parámetros del análisis de fase en Gated-SPECT como predictores independientes de mortalidad en pacientes con enfermedad coronaria avanzada e insuficiencia ventricular izquierda. Materiales y método: Estudio retrospectivo de cohortes históricas de 185 pacientes consecutivos (140 hombres; edad media=67,6±12,7 años) a los que, entre enero de 2009 y marzo de 2011, se les hizo estudio isotópico de perfusión miocárdica con estimulación farmacológica con resultado positivo para isquemia/necrosis con FEVI ≤ 55%. Adicionalmente, se les realizó seguimiento medio de 32,4±10,5 meses registrándose la aparición de eventos cardíacos mayores (infarto agudo de miocardio no mortal, ingreso hospitalario y revascularización coronaria tardía) y mortalidad total. Resultados: Durante el seguimiento se registraron eventos mayores en 51 pacientes así como 28 fallecimientos, de los cuales, 82,1% mostró valores alterados de los parámetros de fase: media=141,1(±17,6(; desviación estándar=15,8(±10,1(; ancho de banda=59,1(±36( y FEVI=42,4%±10,8%. El análisis de Cox mostró al ancho de banda como un predictor independiente de muerte, disminuyendo significativamente la supervivencia y aumentando el riesgo de muerte (hazard ratio=2,68; p<0,05). Conclusiones: El ancho de banda en el análisis de fase se comporta como un predictor independiente de muerte en pacientes con miocardiopatía conocida y FEVI deprimida.

Abstract Background: Coronary disease is one of the main causes of morbidity and mortality in western countries. In the advanced stages of the disease the myocardial remodelling processes can lead to progressive heart failure and left ventricular impairment. The phase analysis of Gated-SPECT studies of myocardial perfusion show parameters that have been characterised as valid marker of ventricular asynchrony. Objective: To evaluate the phase analysis parameters in Gated SPECT as independent predictors of mortality in patients with advanced coronary disease and left ventricular failure. Materials and method: A retrospective historic cohort study was conducted on 185 consecutive patients (140 males; mean age = 67.6±12.7 years) on whom, between January 2009 and March 2011, an isotope myocardial perfusion study was carried out with pharmacologic stimulation and with a positive result for ischaemia / necrosis, and with a LVEF ≤ 55%. A mean follow-up of 32.4 ±10.5 months was also performed, recording the appearance of major cardiac events (non-fatal acute myocardial infarctions, hospital admission, delayed coronary revascularisation, and total mortality. Results: Major events were recorded in 51 patients during follow-up. There were also 28 deaths, of which 82.1% showed abnormal values of the phase parameters: media=141.1(±17.6(; standard deviation=15.8(±10.1(; bandwidth=59.1(±36(, and LVEF = 42.4%±10.8%. The Cox analysis showed the bandwidth as an independent predictor of death, significantly reducing the survival and increasing the risk of death (hazard ratio=2.68; P<.05). Conclusions: The bandwidth in the phase analysis behaves as an independent predictive factor in patients with known myocardial disease and an impaired LVEF.

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Resumen Introducción y objetivos: El análisis de fase mediante Gated-SPECT de perfusión miocárdica (GS-PMI) es una nueva herramienta para medir la asincronía ventricular izquierda con importantes aplicaciones clínicas futuras en resincronización e insuficiencia cardiaca. Se puede medir mediante dos programas (ECTb o QGS C-S). El objetivo es demostrar su factibilidad y verificar si existen diferencias entre ambos. Metodología: Estudio analítico, observacional y retrospectivo en pacientes con GS-PMI normales. Los parámetros obtenidos fueron: la desviación estándar de la fase (DE) y el ancho de banda de histograma (AH). La evaluación de la diferencia entre los grupos se realizó usando pruebas para muestras independientes después de analizar la distribución de datos. Nivel de significación p<0,05. Se utilizó SPSS IBM V.21®. Resultados: Total pacientes: 193 (104 hombres). Edad media: 64 años (24-89).61/193 procesados con QGS C-S y 132/193 con ECTb. Postestrés: la media de la DE fue 6º±3,7º, con mediana de 5º y rango intercuartílico (IR):3.6º. La media de AH fue 22,7º±10º, con mediana de 18º y IR:11.5º. Postreposo: la media de la DE fue 5,76º±4,82º y la mediana 4,5º con IR: 3.1º. La media de AH fue 21.67º± 14.06º y la mediana 18º, IR:12º. Entre ambos programas se encontraron diferencias significativas en la DE en postestrés (p=0,001) y postreposo (p=0,019), sin diferencias en el AH postestrés (p=0,31) y postreposo (p=0,18). Conclusión: Realizar el análisis fase de análisis por GS-PMI es factible. Sin embargo, la DE mostró diferencias significativas entre los dos programas. Aunque los valores mostrados podrían ser utilizados como valores normales, se recomienda que estos se obtengan y utilicen para cada programa por separado.

Abstract Introduction and objectives:Phase analysis by Gated-SPECT myocardial perfusion imaging (G-MPI) is a new tool to measure left ventricular dyssynchrony with important clinical applications in near future (heart failure and resynchronization) and can be measured by two software (ECTb o QGS C-S). The aim is to show its feasibility and verify whether there is difference between the programs. Methodology: Analytical observational and retrospective study in patients with normal G-MPI. The parameters were the phase standard deviation (SD) and the histogram bandwidth (HB) in post-stress and rest tests. Assessment of the difference between groups was performed using tests for independent samples after analyze the distribution of data. The significance level (p) was 0,05 and the software used was SPSS IBM V.21® Results: Total:193 patients (104 men).64 years old ± (24-89).61/193 processed with QGS C-S and 132/193 with ECTb. Post-stress tests: mean of the SD was 6º±3.7º,the median was 5º,interquartile range (IR):3.6º.The mean of HB was 22.7º±10º and the median was 18º IR:11.5º. Post-rest tests: mean of the SD was 5.76º±4.82º and median was 4.5º IR: 3.1º.The overall mean of HB was 21.67º±14.06º and median was 18º IR: 12º. Between the data from both software, significant differences were found in SD in post-stress(p=0.001)and post-rest tests(p=0.019)and no significant differences were found in HB in post-stress(p= 0.31)or post-rest tests(p=0.18). Conclusion: Phase analysis by G-MPI is feasible. However SD showed significant differences between the two groups. Although the values showed could be used as normal values, it is recommended that these have to be obtained and used for each software separately.

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Left ventricular dyssynchrony (LVD) is an independent predictor of adverse cardiovascular events, death, and progression to heart failure. Myocardial perfusion imaging (MPI) with ECG-gated single-photon emission computed tomography (SPECT) can be used to diagnose LVD rapidly and automatically using phase analysis (PA). The objective of this study was to evaluate the prevalence and predictors of LVD in patients undergoing MPI. Clinical, electrocardiographic, and scintigraphic data from 1000 patients who underwent MPI with ECG-gated SPECT over a period of 1 year were analyzed retrospectively. TheEmoryCardiac Toolboxsoftware was used for PA, and LVD was diagnosed based on the following criteria: standard deviation of LV phase distribution ≥43° and/or phase histogram ≥140° in the resting and/or stress phase of the examination. Several variables were evaluated using univariate and multivariate analyses. The prevalence of LVD in the study population was 6.5 %, and the average age was 63.6 ± 12 years. The variables significantly associated with LVD were male gender, obesity, hypertension, diabetes, dyslipidemia, coronary artery disease (CAD), QRS interval ≥120 ms, LV dysfunction, and myocardial perfusion defects (especially fixed defects) on MPI. Although the PA parameters were greater at rest, both phases could be used for diagnosis. Multivariate analysis revealed that the variables significantly associated with LVD were male sex, obesity, history of CAD, and QRS interval ≥120 ms. The overall prevalence of LVD was 6.5 % in patients undergoing MPI in this study, and it reached 42 % in the presence of certain risk factors.

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Study of polymorphism is of great importance for the pharmaceutical industry once polymorphs may display different physicochemical properties, which, in turn, may result in stability differences that can bring problems for the manufacturing stages and the quality of fnal products. Although research on organic polymorphs has greatly increased in the last decades, it still does not cover all needs for the pharmaceutical market. Techniques such as spectroscopy in the infrared region, nuclear magnetic resonance, thermal analysis, X-ray diffraction, etc., can be used to identify polymorphism. The polymorphism is a property of the crystalline solid state, and can be evaluated by X-ray diffraction once each polymorph exhibits one specifc X-ray diffraction pattern. The JST-XRD program is a tool designed to help the identifcation of crystalline phases (including polymorphs) present in pharmaceutical ingredients and tablets by using X-ray diffraction data obtained from scientifc articles and patents. This paper presents new implementations for the JST-XRD and describes its use in the analysis of active pharmaceutical ingredient and marketed tablets of norfloxacin, mebendazole and atorvastatin calcium. By the means of comparison, JSTXRD allowed identifying the crystalline phases in the diffraction patterns of the analyzed drugs, showing the program suitability for polymorphism research, pre-formulation and quality control in pharmaceutical industries. JST-XRD can also be used for educational purposes in undergraduate and graduate programs in order to show the potentiality of X-ray powder diffraction in polymorphism analysis.(AU)

O estudo do polimorfsmo é de grande importância na indústria farmacêutica porque os polimorfos podem apresentar diferentes propriedades físico-químicas, podendo resultar em diferenças na estabilidade e desse modo causar problemas nas etapas de manufatura e no produto fnal. Embora a pesquisa de moléculas orgânicas que apresentam polimorfsmo tenha aumentado bastante nas últimas décadas, ainda não contempla todas as necessidades do mercado farmacêutico. Para a identifcação de polimorfsmo podem ser utilizadas técnicas como espectroscopia na região do infravermelho, ressonância nuclear magnética, análise térmica (DSC), difração de raios X, etc. O polimorfsmo, por ser uma propriedade do estado sólido e cristalino, pode ser avaliado através da difração de raios X, já que cada polimorfo apresenta um padrão de difração de raios X único. O programa JST-XRD é uma ferramenta projetada para auxiliar a identifcação de fases cristalinas, incluindo polimorfos, presentes em insumos farmacêuticos e comprimidos, usando dados de difração de raios X obtidos em artigos científcos e patentes. Esse trabalho apresenta novas implementações no JST-XRD e descreve seu uso na análise de amostras de princípio ativo e comprimidos comerciais de norfloxacino, mebendazol e atorvastatina cálcica. Através das comparações realizadas, JSTXRD permitiu identifcar todas as fases cristalinas dos difratogramas dos fármacos analisados, mostrando que o programa é adequado para pesquisa em polimorfsmo; na pré-formulação e controle de qualidade em indústrias farmacêuticas, assim como para uso didático em cursos de graduação e pós-graduação a fm de mostrar as potencialidades da difração de raios X na análise de polimorfsmo.(AU)

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Finasteride (FNT) is a drug that inhibits human enzyme type II 5α-reductase that metabolizes testosterone into dihydrotestosterone. There are two enantiotropic polymorphs with known crystal structure: designated as forms I and II. Identification and control of these polymorphic forms in mixtures can be performed using X-ray powder diffraction (XRPD) data and Rietveld method (RM). As experimental conditions may limit the detection of minority phases in mixtures, it is interesting to show what are these limits for some usual and one high-resolution equipment. So, in this work, we discuss the parameters to find the limit of the detection in binary mixtures of forms I and II of FNT according to each experimental condition. The samples analyzed were binary mixtures prepared with anhydrous polymorphs of the drug FNT. These samples were measured in four diffractometers with different experimental condition. These equipments represent the main resolutions generally used for drug analysis by XRPD. For the development of this work, a batch of form I was obtained pure, and another batch with forms I and II was used to obtain pure form II by heat treatment. Depending on the experimental condition, the polymorphs could be detected in a proportion as low as 0.5 wt%. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3567-3575, 2014.

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The cuticle of plants that covers the epidermis of cells, an interface between the fruit and the environment, has an important role to play in fruit quality because it prevents water loss and mechanical damage while simultaneously forming a barrier as it prevents phytopathogens from entering the fruit. All these factors give rise to flaws in the appearance of the fruit, thus contributing to marketing problems in the form of financial loss. In the search for solutions to some of these problems, certain biocontrolling yeasts have been introduced in the last few years. In the study described here, the changes observed on the surface of the whole tomato were evaluated in vivo during the first 72 h after inoculation by spraying Candida guilliermondii yeast onto the fruit's surface. The measurements were taken on a nanometric scale using atomic force microscopy; images were created in both contact and tapping modes. The results showed diminished roughness of the surface, which could contribute to reduced phytopathogen adherence due to the thinner contact area. These results furthermore showed that a yeast biofilm was formed on the fruit which probably helps to improve water retention inside the fruit.

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