Ajustando a RFR por Preditores de Discordância, "A RFR Ajustada": Uma Metodologia Alternativa para Melhorar a Capacidade Diagnóstica dos Índices Coronarianos / Adjusting RFR by Predictors of Disagreement, "The Adjusted RFR": An Alternative Methodology to Improve the Diagnostic Capacity of Coronary Indices

Resumo Fundamento Os limiares de corte para a "relação do ciclo completo de repouso" (RFR) oscilam em diferentes séries, sugerindo que as características da população podem influenciá-los. Da mesma forma, foram documentados preditores de discordância entre a RFR e a reserva de fluxo fracionado (FFR). O Estudo RECOPA, mostrou que a capacidade diagnóstica está reduzida na "zona cinzenta" da RFR, tornando necessária a realização de FFR para descartar ou confirmar isquemia. Objetivos Determinar os preditores de discordância, integrar as informações que eles fornecem em um índice clínico-fisiológico: a "RFR Ajustada", e comparar sua concordância com o FFR. Métodos Usando dados do Estudo RECOPA, os preditores de discordância em relação à FFR foram determinados na "zona cinzenta" da RFR (0,86 a 0,92) para construir um índice ("RFR Ajustada") que pesaria a RFR juntamente com os preditores de discordância e avaliar sua concordância com a FFR. Resultados Foram avaliadas 156 lesões em 141 pacientes. Os preditores de discordância foram: doença renal crônica, cardiopatia isquêmica prévia, lesões não envolvendo a artéria descendente anterior esquerda e síndrome coronariana aguda. Embora limitada, a "RFR Ajustada" melhorou a capacidade diagnóstica em comparação com a RFR na "zona cinzenta" (AUC-RFR = 0,651 versus AUC-"RFR Ajustada" = 0,749), mostrando também uma melhora em todos os índices diagnósticos quando foram estabelecidos limiares de corte otimizados (sensibilidade: 59% a 68%; especificidade: 62% a 75%; acurácia diagnóstica: 60% a 71%; razão de verossimilhança positiva: 1,51 a 2,34; razão de verossimilhança negativa: 0,64 a 0,37). Conclusões Ajustar a RFR integrando as informações fornecidas pelos preditores de discordância para obter a "RFR Ajustada" melhorou a capacidade diagnóstica em nossa população. Mais estudos são necessários para avaliar se os índices clínico-fisiológicos melhoram a capacidade diagnóstica da RFR ou de outros índices coronarianos.

Abstract Background Cutoff thresholds for the "resting full-cycle ratio" (RFR) oscillate in different series, suggesting that population characteristics may influence them. Likewise, predictors of discordance between the RFR and fractional flow reserve (FFR) have been documented. The RECOPA Study showed that diagnostic capacity is reduced in the RFR "grey zone", requiring the performance of FFR to rule out or confirm ischemia. Objectives To determine predictors of discordance, integrate the information they provide in a clinical-physiological index, the "Adjusted RFR", and compare its agreement with the FFR. Methods Using data from the RECOPA Study, predictors of discordance with respect to FFR were determined in the RFR "grey zone" (0.86 to 0.92) to construct an index ("Adjusted RFR") that would weigh RFR together with predictors of discordance and evaluate its agreement with FFR. Results A total of 156 lesions were evaluated in 141 patients. Predictors of discordance were: chronic kidney disease, previous ischemic heart disease, lesions not involving the anterior descending artery, and acute coronary syndrome. Though limited, the "Adjusted RFR" improved the diagnostic capacity compared to the RFR in the "grey zone" (AUC-RFR = 0.651 versus AUC-"Adjusted RFR" = 0.749), also showing an improvement in all diagnostic indices when optimal cutoff thresholds were established (sensitivity: 59% to 68%; specificity: 62% to 75%; diagnostic accuracy: 60% to 71%; positive likelihood ratio: 1.51 to 2.34; negative likelihood ratio: 0.64 to 0.37). Conclusions Adjusting the RFR by integrating the information provided by predictors of discordance to obtain the "Adjusted RFR" improved the diagnostic capacity in our population. Further studies are required to evaluate whether clinical-physiological indices improve the diagnostic capacity of RFR or other coronary indices.

Long-Term Vascular Function in CTO Recanalization: A Randomized Clinical Trial of Ticagrelor vs. Clopidogrel.

BACKGROUND: Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel. It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT). METHODS: The TIGER is a prospective, open-label, two parallel-group controlled clinical trial, which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up. RESULTS: Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively) and Doppler data was available in 35 (70%). A high CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p = 0.027), was maintained at follow-up (AUC 34815.22 ± 24,206.06 vs. AUC 22712.47 ± 13,768.95; p = 0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p = 0.933), clopidogrel loading dose-related CBF increased at follow-up (p = 0.039). CONCLUSION: The TIGER trial showed that DAPT with ticagrelor maintained a non-significantly higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with a significant increase at follow-up. The clinical value of such sustained high coronary flow should be evaluated in a larger group of patients. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02211066 (ClinicalTrials.gov number NCT02211066).

Usefulness of the Hybrid RFR-FFR Approach: Results of a Prospective and Multicenter Analysis of Diagnostic Agreement between RFR and FFR-The RECOPA (REsting Full-Cycle Ratio Comparation versus Fractional Flow Reserve (A Prospective Validation)) Study.

BACKGROUND: The resting full-cycle ratio (RFR) is a novel resting index which in contrast to the gold standard (fractional flow reserve (FFR)) does not require maximum hyperemia induction. The objectives of this study were to evaluate the agreement between RFR and FFR with the currently recommended thresholds and to design a hybrid RFR-FFR ischemia detection strategy, allowing a reduction of coronary vasodilator use. MATERIALS AND METHODS: Patients subjected to invasive physiological study in 9 Spanish centers were prospectively recruited between April 2019 and March 2020. Sensitivity and specificity studies were made to assess diagnostic accuracy between the recommended levels of RFR ≤0.89 and FFR ≤0.80 (primary objective) and to determine the RFR "grey zone" in order to define a hybrid strategy with FFR affording 95% global agreement compared with FFR alone (secondary objective). RESULTS: A total of 380 lesions were evaluated in 311 patients. Significant correlation was observed (R 2 = 0.81; P < 0.001) between the two techniques, with 79% agreement between RFR ≤ 0.89 and FFR ≤ 0.80 (positive predictive value, 68%, and negative predictive value, 80%). The hybrid RFR-FFR strategy, administering only adenosine in the "grey zone" (RFR: 0.86 to 0.92), exhibited an agreement of over 95% with FFR, with high predictive values (positive predictive value, 91%, and negative predictive value, 92%), reducing the need for vasodilators by 58%. CONCLUSIONS: Dichotomous agreement between RFR and FFR with the recommended thresholds is significant but limited. The adoption of a hybrid RFR-FFR strategy affords very high agreement, with minimization of vasodilator use.

A Polymorphism Within the MBP Gene Is Associated With a Higher Relapse Number in Male Patients of Multiple Sclerosis.

Myelin basic protein (MBP) is thought to be one of the key autoantigens in multiple sclerosis (MS) development. A recent study described the association of the single nucleotide polymorphism (SNP) rs12959006, within the MBP gene, with a higher risk of relapse and worse prognosis. We aim at studying potential associations of this SNP to MS in an independent population. Clinical data of the first 5 years of the disease were collected retrospectively from 291 MS confirmed patients. MBP polymorphism rs12959006 was genotyped in all patients. Associations with EDSS, number of relapses and serology for Herpesvirus 6 (HHV-6) and Epstein Barr (EBV) viruses were studied. Lymphocyte activation measured by CD69 expression was also analyzed according to sex and rs12959006 genotype. The rs12959006 polymorphism contributed significantly to a higher number of relapses at 5 years after onset only in male patients (rs12959006∗TT ß = 0.74 [0.36-1.09]; p = 7 × 10-5). Titers of anti-HHV6 IgG antibodies showed also a mild association with relapses, both in male and female patients (ß = 0.01 [0.01-0.02]; p = 3.7 × 10-8). Both the genetic variation in MBP and HHV-6 infection aid in predicting a higher number of relapses during the first years of MS. The association described in MBP rs12959006∗T is exclusive to male patients.

Effects of Two Training Modalities on Body Fat and Insulin Resistance in Postmenopausal Women.

Henríquez, S, Monsalves-Alvarez, M, Jimenez, T, Barrera, G, Hirsch, S, de la Maza, MP, Leiva, L, Rodriguez, JM, Silva, C, and Bunout, D. Effects of two training modalities on body fat and insulin resistance in postmenopausal women. J Strength Cond Res 31(11): 2955-2964, 2017-Our objective was to compare the effects of a low-load circuit resistance training protocol and usual aerobic training in postmenopausal women. Postmenopausal women with at least 1 feature of the metabolic syndrome were randomly allocated to a low-load circuit resistance training protocol or traditional aerobic training in a braked cycle ergometer. The intervention consisted in supervised sessions lasting 40 minutes, 3 times per week, during 6 months. At baseline and at the end of the intervention, fasting serum lipid levels, serum interleukin 6, C-reactive protein, 8 isoprostanes, and insulin resistance (assessed through QUICKI and HOMA-IR) were measured. Body fat was measured by double-beam X-ray absorptiometry and by computed tomography densitometric quantification at lumbar 3 vertebral level. Twenty-one women aged 58 (54-59) years were allocated to aerobic training and 21 women aged 55 (52-61) years were allocated to the low-load circuit resistance training protocol. Eighteen and 16 women in each group completed the 6 months training period. Women in both groups experienced significant reductions in blood pressure, total body, subcutaneous, and intraabdominal body fat. Reductions in total cholesterol and triacylglycerol levels were also observed. No changes in insulin resistance indexes, 8 isoprostanes, C-reactive protein, or interleukin 6 were observed in either group. No significant differences between treatment groups were observed in any of the measured parameters. We conclude that low-load circuit resistance training and aerobic training resulted in the same reductions in body fat and serum lipid levels.

Irisin is weakly associated with usual physical activity in young overweight women

PURPOSE: To determine if irisin plasma levels are associated with regular physical activity, body composition and metabolic parameters in women subjected to calorie restriction. SUBJECTS AND METHODS: We studied 42 women aged 34 ± 13 years with a body mass index of 27.7 ± 1.8 kg/m2, who were subjected to a calorie restriction for three months. At baseline and at the end of the study, weight, waist and hip circumference, laboratory parameters, body composition by DEXA, resting and activity energy expenditure by indirect calorimetry and 72 hours actigraphy were measured. Fasting serum irisin was quantified using an ELISA kit. RESULTS: After the intervention period, participants lost 1.5 (0.4-3.4) kg and irisin levels did not change. Irisin baseline levels were positively but weakly correlated with the level of physical activity. This association was lost at the end of the intervention. No association was found between irisin levels and body composition or insulin sensitivity or their changes after calorie restriction. No association between serum irisin levels and PGC-1αexpression in peripheral blood mononuclear cells and serum irisin was observed. CONCLUSIONS: Fasting serum irisin was weakly associated with usual physical activity and did not change after calorie restriction.

Impact of ancient cereals, pseudocereals and legumes on starch hydrolysis and antiradical activity of technologically viable blended breads.

Wheat flour replacement from 22.5% up to 45% by incorporation of ternary blends of teff (T), green pea (GP) and buckwheat (BW) flours provided technologically viable and acceptable sensory rated multigrain breads with superior nutritional value compared to the 100% wheat flour (WT) counterparts. Blended breads exhibited superior nutritional composition, larger amounts of bioaccessible polyphenols, higher anti-radical activity, and lower and slower starch digestibility. Simultaneous lower rapidly digestible starch (57.1%) and higher slowly digestible starch (12.9%) and resistant starch (2.8%) contents (g per 100g fresh bread), considered suitable nutritional trends for dietary starch fractions, were met by the blend formulated 7.5% T, 15% GP, 15% BK. The associated mixture that replaced 37.5% WT, showed a rather lower extent and slower rate of starch hydrolysis with medium-low values for C∞, and H90, and lowest k, and intermediate expected Glycaemic Index (86). All multigrain breads can be labelled as source of dietary fibre (≥ 3 g dietary fibre/100g bread).

ST proteins, a new family of plant tandem repeat proteins with a DUF2775 domain mainly found in Fabaceae and Asteraceae.

BACKGROUND: Many proteins with tandem repeats in their sequence have been described and classified according to the length of the repeats: I) Repeats of short oligopeptides (from 2 to 20 amino acids), including structural cell wall proteins and arabinogalactan proteins. II) Repeats that range in length from 20 to 40 residues, including proteins with a well-established three-dimensional structure often involved in mediating protein-protein interactions. (III) Longer repeats in the order of 100 amino acids that constitute structurally and functionally independent units. Here we analyse ShooT specific (ST) proteins, a family of proteins with tandem repeats of unknown function that were first found in Leguminosae, and their possible similarities to other proteins with tandem repeats. RESULTS: ST protein sequences were only found in dicotyledonous plants, limited to several plant families, mainly the Fabaceae and the Asteraceae. ST mRNAs accumulate mainly in the roots and under biotic interactions. Most ST proteins have one or several Domain(s) of Unknown Function 2775 (DUF2775). All deduced ST proteins have a signal peptide, indicating that these proteins enter the secretory pathway, and the mature proteins have tandem repeat oligopeptides that share a hexapeptide (E/D)FEPRP followed by 4 partially conserved amino acids, which could determine a putative N-glycosylation signal, and a fully conserved tyrosine. In a phylogenetic tree, the sequences clade according to taxonomic group. A possible involvement in symbiosis and abiotic stress as well as in plant cell elongation is suggested, although different STs could play different roles in plant development. CONCLUSIONS: We describe a new family of proteins called ST whose presence is limited to the plant kingdom, specifically to a few families of dicotyledonous plants. They present 20 to 40 amino acid tandem repeat sequences with different characteristics (signal peptide, DUF2775 domain, conservative repeat regions) from the described group of 20 to 40 amino acid tandem repeat proteins and also from known cell wall proteins with repeat sequences. Several putative roles in plant physiology can be inferred from the characteristics found.

Two cell wall Kunitz trypsin inhibitors in chickpea during seed germination and seedling growth.

Two Kunitz trypsin inhibitors TPI-1 and TPI-2, encoded by CaTPI-1 and CaTPI-2, previously identified and characterized, have been detected in chickpea (Cicer arietinum L.) embryonic axes from seeds imbibed up to 48 h. Their gene transcription commenced before germination sensu stricto was completed. The transcript amount of CaTPI-1 remained high until 24 h after imbibition, when the epicotyls started to grow, while CaTPI-2 mRNA, which appeared later, reached a maximum at 48 h. Both the temporal and the spatial distribution of TPI-1 and TPI-2 proteins in the embryonic axes suggest that they perform different functions. The early appearance of TPI-1 in imbibed seeds suggests that it plays a protective role, preventing the premature degradation of the proteins stored in the embryonic axes. Its pattern of distribution suggests that the protein is involved in the regulation of vascular tissue differentiation, protecting the cells from some proteinases involved in programmed cell death. With regard to TPI-2, its later synthesis after imbibition, together with its tissue distribution, indicates that it is mainly active following germination, during elongation of the embryonic axes.

The accumulation of a Kunitz trypsin inhibitor from chickpea (TPI-2) located in cell walls is increased in wounded leaves and elongating epicotyls.

Here, we report the identification and characterization of CaTPI-2, which is a member of a Cicer arietinum gene family encoding Kunitz-type proteinase inhibitors with at least two members -CaTPI-1 and CaTPI-2. The widespread mRNA accumulation of CaTPI-2 in all the different organs of 4-day-old etiolated seedlings and in stem internodes differs from the more specific Cicer arietinum Trypsin Proteinase Inhibitor-1 (CaTPI-1) transcription. After the generation of polyclonal antibodies against the recombinant Trypsin Proteinase Inhibitor-2 (TPI-2) protein, the protein was located in the cell walls of vegetative organs. The decrease found in both transcription and TPI-2 protein levels when the epicotyls aged, together with the wider and more intensive immunostaining of the protein in apical zones of epicotyls and radicles, in consonance with their higher elongation rate, indicated a relationship of the TPI-2 protein with the elongation process. CaTPI-2 mRNA levels were increased by wounding in both epicotyls and leaves. The accumulation of CaTPI-2 mRNA in seedlings, which was further amplified by mechanical wounding in epicotyls and leaves, suggests the involvement of TPI-2 in the response to wounds. Our results indicate that TPI-2 protein has features different from those of the former characterized Trypsin Proteinase Inhibitor-1 (TPI-1), such as its different gene regulation under light, a different cellular location and its upregulation by wounding, which implies a function different from that of TPI-1 in chickpea metabolism.

Comunicación familiar y comportamientos delictivos en adolescentes españoles: el doble rol mediador de la autoestima / Family communication and delinquent behavior among spanish adolescents: the mediating role of self-esteem

This research analyses the relationship among family communication (open communication versus communication problems), multidimensional self-esteem (family, academic, social and physical self-esteem) and behavioural problems in adolescence. Two independent samples were used in the study: Sample 1 was composed of 414 adolescents ranging in age from 12 to 17 years old, and Sample 2 was composed of 625 adolescents aged from 11 to 20 years old. Results showed an indirect effect of family communication on delinquent behavior through the mediation of self-esteem. We found a protection effect of family and academic self-esteem and a risk effect of social and physical self-esteem on delinquent behavior.

El presente estudio analiza las relaciones entre la comunicación familiar (comunicación abierta o problemática), la autoestima considerada desde una perspectiva multidimensional (autoestima familiar, escolar, social y física) y los comportamientos delictivos en adolescentes. Se utilizan dos muestras independientes: la primera está constituida por 414 chicas y chicos de 12 a 17 años y la segunda por 625 chicas y chicos de 11 a 20 años. Se observa, en las dos muestras, una influencia indirecta de la comunicación familiar en el comportamiento delictivo a través de una mediación de la autoestima. Además, se observa, tanto un efecto protector de las autoestimas familiar y escolar frente a la implicación en comportamientos delictivos, como un efecto de riesgo de las autoestimas social y física.

Funcionamiento familiar, autoestima y consumo de sustancias en adolescentes: un modelo de mediación / Family functioning, self-esteem and substance use in adolescents: a mediational model

OBJETIVO: Analizar las relaciones directas e indirectas entre el funcionamiento familiar, la autoestima considerada desde una perspectiva multidimensional (autoestima familiar, escolar, social y física) y el consumo de sustancias. MATERIAL Y MÉTODOS: Los datos se recogieron durante el año escolar 2003-2004 y corresponden a dos muestras independientes de adolescentes españoles (n1= 414, Castilla y León; n2= 625, Comunidad Valenciana). Para el análisis de datos se utilizó la técnica estadística de ecuaciones estructurales y se siguió el procedimiento de análisis de efectos mediadores de Holmbeck (1997). RESULTADOS: La autoestima media significativamente la influencia del funcionamiento familiar en el consumo de sustancias de los adolescentes. Además, se observa, por un lado, un efecto protector de las autoestimas familiar y escolar frente a la implicación en el consumo de sustancias y, por otro, un efecto de riesgo de las autoestimas social y física. CONCLUSIONES: Parece necesario adoptar una perspectiva multidimensional en el estudio de la autoestima de adolescentes consumidores y prevenir la sobrevaloración en las dimensiones social y física.

OBJECTIVE: This research analyzes the direct and indirect relationships among family functioning, multidimensional self-esteem (family, academic, social, and physical self-esteem) and substance use. MATERIALS AND METHODS: The study participants were composed of two independent samples of Spanish adolescents who provided information during the 2003-2004 academic year (n1= 414, Castilla & León; n2= 625, Comunidad Valenciana). The statistical analyses were carried out using structural equation modelling and the procedure of mediation effects analysis (Holmbeck, 1997). RESULTS: Results showed a significant mediational effect of self-esteem on the relation between family functioning and adolescent substance use. Moreover, results showed, on the one hand, a protection effect of family and academic self-esteem in the face of substance use and, on the other hand, a risk effect of social and physical self-esteem. CONCLUSIONS: It is necessary to adopt a multidimensional perspective when analyzing the self-esteem of adolescents with substance use and to prevent the over-valuation of social and physical dimensions.

Factors that influence platelet recovery after transfusion: resolving donor quality from ABO compatibility.

BACKGROUND: A system was established to examine the extent to which the apheresis donor determines platelet recovery after transfusion, to measure the impact of ABO identity, and to predict outcome by evaluating the donor. STUDY DESIGN AND METHODS: The percentage of platelet recovery was measured after prophylactic transfusion of apheresis units divided from single donors to paired recipients with uncomplicated thrombocytopenia secondary to leukemia chemotherapy. Platelet microaggregation induced by citrate was measured at the time of apheresis. RESULTS: Platelet recoveries in paired recipients correlated strongly when both transfusions were ABO- identical. When one recipient was ABO-identical and the other was ABO-nonidentical, nonidentical transfusions yielded one-third the recovery of ABO-identical transfusions. In ABO-identical transfusions, platelet recovery in donors having microaggregates in the before-apheresis ACD sample was one-third that in donors without microaggregates. This difference was observed at 1 and 24 hours. Expression of P-selectin in the apheresis units at the time of transfusion correlated well with ACD microaggregates in the before-apheresis sample. CONCLUSION: When transfusions of platelets are ABO-identical, donor quality dominates recovery in circulation. Donor quality is predicted by a rapid and simple assay of citrate-induced microaggregation performed at the time of apheresis. When donor quality is factored out, ABO identity prevails.

Diagnóstico de la incompetencia cervical por ultrasonido / Ultrasonic diagnosis of cervical incompetence

Se analizaron 30 pacientes con datos anamnésicos y clínicos de incompetencia cervical; en 25 de ellas (83,3 %) se diagnosticó insuficiencia del orificio cervical interno. En nuestro trabajo catalogamos como de mal pronóstico el acortamiento del cuello. Debemos señalar que existen críterios en las bibliografías revisadas, acerca del valor del acortamiento del cuello para el pronóstico desfavorable. Los parámetros medidos en el estudio ultrasónico fueron: longitud del cuello, diámetro del canal cervical y estrechamiento del segmento inferior interno. Lo parámetros encontrados en nuestra casuística coinciden con la bibliografía. Por tratarse de un estudio prospectivo es necesario analizar la evolución de las gestantes para llegar a conclusiones definitivas

Analysis by fluorescence microscopy and flow cytometry of Monoclonal antibodies produced against cell surface antigens

La reactividad de siete anticuerpos monoclonales contra antígenos de superficie de las células de mieloma Sp2/O-Ag14 fue analizada simultáneamente por microscopía de fluorescencia y por citometría de flujo. Se incubaron 1 x 10**6 células de Sp2/O-Ag14 con 200 micronl de anticuerpo monoclonal a 4-C por 30 min. Luego de lavar 2 veces con PBS las células fueron incubadas a 4-C por 30 minutos con una dilución 1:400 de anticuerpos de carnero anti-immunoglobulinas de ratón, conjugados a isotiocianato de fluoresceína. Luego de lavar tres veces con PBS, las células se utilizaron para el análisis. Por microscoía de fluorescencia se detectaron diferentes patrones de reactividad con los anticuerpos monoclonales. Estos patrones fueron denominados: homogéneo anular, parchos anulares, parchos putiformes, difuso y homogéneo. Estos patrones podrían representar diferentes espítopes reconocidos monoclonales contra los antígenos de superficie de Sp2/O-Ag14 varió entre un 79 a un 90% al analizarse por cimetría de flujo con el sistema EPICS V. Al compararla con la microscopía de fluorescencia, la citometria de flujo determinó de una forma mas rápida, sensitiva y cuantitativa la reactividad de los diferentes anticuerpos monoclonales contra antígenos de superficie de las células Sp2/O-Ag14