Exploring the applicability of a lesion segmentation method on [18F]fluorothymidine PET/CT images in diffuse large B-cell lymphoma.

BACKGROUND AND PURPOSE: The determination of the total metabolic tumour volume based on [18F]fluorothymidine ([18F]FLT) PET/CT images in diffuse large B-cell lymphoma has a potential clinical value for detecting early relapse in this type of heterogeneous lymphoproliferative tumours. Tumour segmentation is a key step in this process. For this purpose, our objective was to determine a segmentation threshold of [18F]FLT PET/CT images, based on a reference tissue uptake, on a cohort of patients with diffuse large B-cell lymphoma (DLBCL) that have been scanned at different stages of the treatment. METHODS: We enrolled 23 adult patients with DLBCL confirmed in II-IV stages without nervous system compromise. All patients were scanned using [18F]FLT PET/CT at the time of diagnosis (baseline PET), interim PET (iPET), and at the end of treatment (fPET). The administered activity was 1.8-2.6 MBq/kg body weight, performed 60-70 min after injection and without use of contrast-enhanced CT. First, we assessed the [18F]FLT uptake stability in liver and bone marrow along the patient follow-up. For the lesion segmentation, three threshold values were assessed. RESULTS: Both, liver, and bone marrow can be indistinctly taken as reference tissue. The SUV threshold for a voxel to be considered as belonging to a lesion is expressed in terms of a percentage relative to the patient's uptake in the reference tissue. Found thresholds were: for liver, 62%, 33%, 27%; and for bone marrow, 35%, 21% and 22%, for baseline, iPET and fPET stages, respectively. The relative threshold throughout the treatment has a decreasing tendency along the stages. CONCLUSION: Based on the results obtained with [18F]FLT PET/CT during staging and follow-up in patients with DLBCL, reference values were obtained for each stage referring to liver and bone marrow uptake that could be used in clinical practice oncology.

A brainstem circuit for the expression of defensive facial reactions in rat.

The brainstem houses neuronal circuits that control homeostasis of vital functions. These include the depth and rate of breathing1,2 and, critically, apnea, a transient cessation of breathing that prevents noxious vapors from entering further into the respiratory tract. Current thinking is that this reflex is mediated by two sensory pathways. One known pathway involves vagal and glossopharyngeal afferents that project to the nucleus of the solitary tract.3,4,5 Yet, apnea induced by electrical stimulation of the nasal epithelium or delivery of ammonia vapors to the nose persists after brainstem transection at the pontomedullary junction, indicating that the circuitry that mediates this reflex is intrinsic to the medulla.6 A second potential pathway, consistent with this observation, involves trigeminal afferents from the nasal cavity that project to the muralis subnucleus of the spinal trigeminal complex.7,8 Notably, the apneic reflex is not dependent on olfaction as it can be initiated even after disruption of olfactory pathways.9 We investigated how subnucleus muralis cells mediate apnea in rat. By means of electrophysiological recordings and lesions in anesthetized rats, we identified a pathway from chemosensors in the nostrils through the muralis subnucleus and onto both the preBötzinger and facial motor nuclei. We then monitored breathing and orofacial reactions upon ammonia delivery near the nostril of alert, head-restrained rats. The apneic reaction was associated with a grimace, characterized by vibrissa protraction, wrinkling of the nose, and squinting of the eyes. Our results show that a brainstem circuit can control facial expressions for nocifensive and potentially pain-inducing stimuli.

Asociación y valor predictivo del índice poder mecánico-distensibilidad pulmonar con días libres de ventilación mecánica en pacientes con COVID-19 en una unidad de terapia intensiva / Association and predictive value of the mechanical power-lung compliance index with free days off mechanical ventilation in patients with COVID-19 in an intensive care unit / Associação e valor preditivo do índice de potência mecânica/complacência pulmonar com dias livres de ventilação mecânica em pacientes com COVID-19 em unidade de terapia intensiva

Resumen: Introducción: El poder mecánico (PM) se asocia a mortalidad y se debe ajustar a las características pulmonares en pacientes COVID-19. Material y métodos: Estudio observacional, retrospectivo y analítico, de septiembre de 2020 a febrero de 2021. Los parámetros de ventilación y análisis de la curva ROC y modelos de regresión de Poisson para OR. Objetivo primario fue determinar la asociación entre el índice PM/Cest y días libres de ventilación mecánica (DLVM). Resultados: Se incluyeron 43 pacientes. Se dividió en sobrevivientes (n = 25, 58.1%) y no sobrevivientes (n = 18, 41.9%). Se eligió mediana de DLVM con los parámetros de VMI. El índice PM/Cest inicial ABC 0.73 [IC 95% (0.58-0.88), p = 0.008], punto de corte de 0.90 Joules/min/mL/cm H2O. La regresión multivariable de Poisson el índice PM/Cest inicial OR 0.18 [IC 95% (0.03-0.98), p = 0.047]. Discusión: Coppola y colaboradores documentaron que en pacientes con SDRA no COVID-19, el valor de PM absoluto no demostró significancia; al ajustarlo a Cest fue independiente para mortalidad. Conclusiones: El índice PM/Cest al inicio se asoció de forma significativa e independiente con DLVM en COVID-19. Punto de corte de 0.9 J/min/mL/cmH2O con mejor sensibilidad y especificidad para predecir los DLVM y esto podría reducir la mortalidad.

Abstract: Introduction: Mechanical power (MP) is associated with mortality and must be adjusted to the pulmonary characteristics in COVID-19 patients. Material and methods: Observational, retrospective, analytical study from September 2020-February 2021. Ventilation parameters and ROC curve analysis and Poisson regression models for OR. Primary objective was to determine the association between the PM/Cest index and free days of mechanical ventilation (FDMV). Results: 43 patients were included. It was divided into survivors (n = 25, 58.1%) and non-survivors (n = 18, 41.9%). Median FDMV was chosen with the IMV parameters. The initial MP/Cest index ABC 0.73 [95% CI (0.58-0.88), p = 0.008], cut-off point of 0.90 J/min/mL/cmH2O. The multivariate Poisson regression showed the initial MP/Cest index OR 0.18 [95% CI (0.03-0.98), p = 0.047]. Discussion: Coppola et al. documented in patients with non-COVID-19 ARDS, the absolute MP value did not demonstrate significance; when adjusted to Cest, it was independent for mortality. Conclusions: The MP/Cest index at baseline was significantly and independently associated with FDMV in COVID-19. Cut-off point of 0.9 J/min/mL/cmH2O with better sensitivity and specificity to predict FDMV and this could reduce mortality.

Resumo: Introdução: A potência mecânica (PM) está associada à mortalidade e deve ser ajustada para características pulmonares em pacientes com COVID-19. Material e métodos: Estudo observacional, retrospectivo, analítico de setembro de 2020 a fevereiro de 2021. Os parâmetros ventilatórios, análise da curva ROC e modelos de regressão de Poisson para OR. O objetivo primário foi determinar a associação entre o índice PM/Cest e dias livres de ventilação mecânica (DLVM). Resultados: Foram incluídos 43 pacientes. Dividiu-se em sobreviventes (n = 25, 58.1%) e não sobreviventes (n = 18, 41.9%). A mediana do DLVM foi escolhida com os parâmetros do VMI. Índice inicial PM/Cest ABC 0.73 [IC 95% (0.58-0.88), p = 0.008], ponto de corte de 0.90 J/min/mL/cmH2O. Regressão multivariável de Poisson no índice PM/Cest inicial OR 0.18 [IC 95% (0.03-0.98), p = 0.047]. Discussão: Coppola et al. documentaram em pacientes com SDRA não-COVID-19, o valor de PM absoluto não mostrou significância; quando ajustado a Cest, foi independente para mortalidade. Conclusões: O índice PM/Cest ao início se associou de maneira significativa e independentemente com DLVM na COVID-19. Ponto de corte de 0.9 J/min/mL/cmH2O com melhor sensibilidade e especificidade para predizer DLVM e isso poderia reduzir a mortalidade.

A vibrissa pathway that activates the limbic system.

Vibrissa sensory inputs play a central role in driving rodent behavior. These inputs transit through the sensory trigeminal nuclei, which give rise to the ascending lemniscal and paralemniscal pathways. While lemniscal projections are somatotopically mapped from brainstem to cortex, those of the paralemniscal pathway are more widely distributed. Yet the extent and topography of paralemniscal projections are unknown, along with the potential role of these projections in controlling behavior. Here, we used viral tracers to map paralemniscal projections. We find that this pathway broadcasts vibrissa-based sensory signals to brainstem regions that are involved in the regulation of autonomic functions and to forebrain regions that are involved in the expression of emotional reactions. We further provide evidence that GABAergic cells of the Kölliker-Fuse nucleus gate trigeminal sensory input in the paralemniscal pathway via a mechanism of presynaptic or extrasynaptic inhibition.

Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients.

Background: SARS-CoV-2 infection has, as of April 2021, affected >133 million people worldwide, causing >2.5 million deaths. Because the large majority of individuals infected with SARS-CoV-2 are asymptomatic, major concerns have been raised about possible long-term consequences of the infection. Methods: Wedeveloped an antigen capture assay to detect SARS-CoV-2 spike protein in urine samples from patients with COVID-19whose diagnosis was confirmed by positive PCR results from nasopharyngeal swabs (NP-PCR+) forSARS-CoV-2. We used a collection of 233 urine samples from 132 participants from Yale New Haven Hospital and the Children's Hospital of Philadelphia that were obtained during the pandemic (106 NP-PCR+ and 26 NP-PCR-), and a collection of 20 urine samples from 20 individuals collected before the pandemic. Results: Our analysis identified 23 out of 91 (25%) NP-PCR+ adult participants with SARS-CoV-2 spike S1 protein in urine (Ur-S+). Interestingly, although all NP-PCR+ children were Ur-S-, one child who was NP-PCR- was found to be positive for spike protein in their urine. Of the 23 adults who were Ur-S+, only one individual showed detectable viral RNA in urine. Our analysis further showed that 24% and 21% of adults who were NP-PCR+ had high levels of albumin and cystatin C, respectively, in their urine. Among individuals with albuminuria (>0.3 mg/mg of creatinine), statistical correlation could be found between albumin and spike protein in urine. Conclusions: Together, our data showed that one of four individuals infected with SARS-CoV-2 develop renal abnormalities, such as albuminuria. Awareness about the long-term effect of these findings is warranted.

Outbreaks of Escherichia coli O157:H7 Infections Linked to Romaine Lettuce in Canada from 2008 to 2018: An Analysis of Food Safety Context.

ABSTRACT: Foodborne diseases are a major cause of illness in Canada. One of the main pathogens causing cases and outbreaks of foodborne illness in Canada is Escherichia coli O157:H7. From 2008 to 2018, 11 outbreaks of E. coli O157:H7 infection in Canada were linked to leafy greens, including 7 (63.6%) linked to romaine lettuce, 2 (18.2%) linked to iceberg lettuce, and 2 (18.2%) linked to other or unspecified types of leafy greens. The consumption of lettuce in Canada, the behavior of E. coli O157:H7 on lettuce leaves, and the production practices used for romaine and iceberg lettuce do not seem to explain why a higher number of outbreaks of E. coli O157:H7 infection were linked to romaine than to iceberg lettuce. However, the difference in the shape of iceberg and romaine lettuce heads could be an important factor. Among the seven outbreaks linked to romaine lettuce in Canada between 2008 and 2018, an eastern distribution of cases was observed. Cases from western provinces were reported only twice. The consumption of romaine and iceberg lettuce by the Canadian population does not seem to explain the eastern distribution of cases observed, but the commercial distribution, travel distances, and the storage practices used for lettuce may be important factors. In the past 10 years, the majority of the outbreaks of E. coli O157:H7 infection linked to romaine lettuce occurred during the spring (March to June) and fall (September to December). The timing of these outbreaks may be explained by the availability of lettuce in Canada, the growing region transition periods in the United States, and the seasonality in the prevalence of E. coli O157:H7. The consumption of romaine lettuce by the Canadian population does not explain the timing of the outbreaks observed.

Estimación de las desviaciones volumétricas de dosis entregada vs. planificada durante el tratamiento de hipertiroidismo con 131I: resultados preliminares / Estimation of volumetric dose distribution delivery deviations vs. dose planned in 131I hyperthyroidism treatment: preliminary results

Resumen En 2013, la Asociación Europea de Medicina Nuclear (AEMN) recomendó un "Procedimiento estándar" para desarrollar la dosimetría individual pretratamiento del Hipertiroidismo con 131I basada en la captación y en cinética tiroidea del paciente. Para estimar las desviaciones en la distribución de dosis entregada vs planificada al volumen tiroideo bajo este procedimiento, se desarrolló y verificó una aplicación en Matlab. Esta aplicación desarrolla el ajuste de la farmacocinética tiroidea, los cálculos de actividad acumulada, la estimación de la masa funcional tiroidea, el cálculo de la actividad a administrar para garantizar la dosis prescrita por el médico, y estimar el mapa tridimensional (3D) de dosis y los parámetros estadísticos relacionados que la caracterizan. La aplicación desarrollada se verificó empleando una imagen-maniquí y 6 farmacocinéticas conocidas. Además, se estimaron y verificaron los parámetros dosimétricos de planificación en 6 pacientes con dosis prescritas entre 150-400 Gy (promedio 241,67 Gy). Las distribuciones de actividad acumulada y de dosis absorbida fueron marcadamente heterogéneas. La distribución de dosis 3D mostró desviaciones estándar entre 18,01-27,08 % de la dosis prescrita. Las diferencias entre la dosis máxima y mínima por voxel/MBq de actividad administrada fue de 74-129 %. De acuerdo a los resultados, sólo entre el 50,2 % y 71,4 % de volumen tiroideo se tratará con la dosis prescrita ±20 %. Conclusiones: la dosis administrada al tejido tiroideo es no-homogénea y discrepa significativamente de la prescrita en algunas regiones, situación que requiere estudios posteriores más profundos con el objetivo de optimizar el tratamiento y sus resultados.

Abstract In 2013, the European Association of Nuclear Medicine Dosimetry Committee recommends a "Standard Operational Procedures for Hyperthyroidism Pre-Therapeutic Dosimetry" based on the assessment of the individual 131I uptake and kinetics. To estimate the 3D dose delivery deviations from prescribed dose during patient specific application of this SOP, a computer Matlab application was developed and verified. It was design to execute: radiopharmaceutical curve fitting, cumulated activity calculations, functional thyroid mass estimation, obtain the therapeutic planning activity to warranty the prescribed dose and produce the 3D planning dose map and related dosimetry parameters. 6 patients with 150-400Gy prescribed dose data planning (average 241,67Gy) were analysed using the developed application. The developed system was verify successfully using a test image phantom and 6 known pharmacokinetics data. The tridimensional thyroid volume cumulated activity and dose distributions were heterogeneous. 3D dose distribution showed standard deviations between 18.01-27.08 % of prescribed dose. The differences between maximum and minimum dose value per voxel/MBq were 74-129%. According to the result, between 50,2 % and 71,4 % of patient's thyroid will be treat with a dose of DP±20 % of planned dose, the rest will be overdose or sub dose. Conclusions: the 3D treatment planning dose distribution were completely no-homogenous, the significant difference observed should be study in the future more deeply in order to optimized the hyperthyroidism iodine treatment.

Outbreak of Vibrio parahaemolyticus Associated with Consumption of Raw Oysters in Canada, 2015.

There has been a steady increase in illness incidence of Vibrio parahaemolyticus (Vp). The majority of illnesses are associated with consumption of raw oysters. In the summer of 2015, Canada experienced the largest outbreak associated with the consumption of raw oysters harvested from British Columbia (BC) coastal waters. Case investigation of laboratory-confirmed cases was conducted to collect information on exposures and to assist traceback. Investigations at processors and oyster sampling were conducted. Eighty-two laboratory-confirmed cases of Vp infection were reported between January 1 and October 26, 2015. The majority of the cases were reported in BC, associated with consumption of raw BC oysters in restaurants. Sea surface temperatures were above the historical levels in 2015. This outbreak identified the need to improve surveillance and response to increases in human cases of Vp. This is of particular importance due to the potential for increasing water temperatures and the likelihood of additional outbreaks of Vibrio.

Test de reserva de sangre preoperatorio en cesáreas electivas de bajo riesgo: ¿es realmente necesario? / Pre-operative blood reserve test in low-risk elective cesareans: Is it really necessary?

Objetivo: el test de tipaje y escrutinio se ha postulado en España como la prueba pretransfusional de elección en cirugía programada. Actualmente, solo el 1,1-1,7% de las pacientes a las que se realiza una cesárea precisan transfusión sanguínea. El objetivo fue valorar la necesidad de realizar test de reserva de sangre preoperatorio en las cesáreas electivas de bajo riesgo, atendiendo al análisis racional de sobrereserva, riesgo-beneficio y coste- efectividad e identificando los factores que comportaron una mayor pérdida hemática. Material y métodos: se diseñó un estudio observacional, descriptivo y retrospectivo. Se incluyó a 189 mujeres sometidas a cesárea electiva en el hospital de Dénia en el período entre 2015 y 2016. Todas ellas disponían de un test de reserva de sangre preoperatorio. Se excluyeron las cesáreas urgentes y las pacientes con indicación de cesárea electiva que iniciaron dinámica de parto o rotura prematura de membranas. Resultados: de las 189 cesáreas, únicamente una (0,005%) precisó transfusión sanguínea de manera preoperatoria, por presentar una hemoglobina de 7 g/dl. Todos los indicadores de reserva sanguínea mostraron sobrereserva en cesáreas electivas. El descenso de hemoglobina se asoció a una edad gestacional inferior a 40 semanas, mayor edad materna y mayor hemoglobina preoperatoria. Conclusiones: los datos obtenidos tras el análisis estadístico de la muestra nos han permitido eliminar el test de reserva de sangre preoperatorio en cesáreas electivas de nuestro protocolo. Se mantendrá en los diagnósticos con mayor riesgo de sangrado y según indicación del obstetra y/o anestesiólogo (AU)

Objective: Type and screen test has been implement in Spain as pre-transfusional elective test in programmed surgery. Currently, only 1.1-1.7% of patients undergoing cesarean section require blood transfusion. To assess the need to make a pre-operative blood reserve test in elective cesarean sections based on the rational analysis of over-reserve, risk-benefit and cost-effectiveness and identifying which factors lead to an increase in blood loss. Material and methods: An observational, descriptive and retrospective study was designed. 189 women were included to be operated by an elective cesarean section at Denia’s Hospital, between 2015 and 2016. All of them had a preoperative blood test reserve. Urgent cesarean sections and patients with elective cesarean section indication who started labor contractions or premature rupture of membranes were excluded. Results: Only one of the 189 women included (0.005%) was given a preoperative blood transfusion, because of the hemoglobin level was 7 g/dl. All blood reserve parameters show over-reserve in elective cesarean sections. The decrease of hemoglobin was associated with a gestational age less than 40 weeks, greater maternal age and greater preoperative hemoglobin. Conclusions: Data obtained after statistical analysis of the sample allowed us to remove the blood reserve test in elective cesarean sections of our protocol. It will be kept in diagnoses with greater bleeding risk and according to the obstetrician and/or anesthesiologist indications (AU)

Transducin duplicates in the zebrafish retina and pineal complex: differential specialisation after the teleost tetraploidisation.

Gene duplications provide raw materials that can be selected for functional adaptations by evolutionary mechanisms. We describe here the results of 350 million years of evolution of three functionally related gene families: the alpha, beta and gamma subunits of transducins, the G protein involved in vision. Early vertebrate tetraploidisations resulted in separate transducin heterotrimers: gnat1/gnb1/gngt1 for rods, and gnat2/gnb3/gngt2 for cones. The teleost-specific tetraploidisation generated additional duplicates for gnb1, gnb3 and gngt2. We report here that the duplicates have undergone several types of subfunctionalisation or neofunctionalisation in the zebrafish. We have found that gnb1a and gnb1b are co-expressed at different levels in rods; gnb3a and gnb3b have undergone compartmentalisation restricting gnb3b to the dorsal and medial retina, however, gnb3a expression was detected only at very low levels in both larvae and adult retina; gngt2b expression is restricted to the dorsal and medial retina, whereas gngt2a is expressed ventrally. This dorsoventral distinction could be an adaptation to protect the lower part of the retina from intense light damage. The ontogenetic analysis shows earlier onset of expression in the pineal complex than in the retina, in accordance with its earlier maturation. Additionally, gnb1a but not gnb1b is expressed in the pineal complex, and gnb3b and gngt2b are transiently expressed in the pineal during ontogeny, thus showing partial temporal subfunctionalisation. These retina-pineal distinctions presumably reflect their distinct functional roles in vision and circadian rhythmicity. In summary, this study describes several functional differences between transducin gene duplicates resulting from the teleost-specific tetraploidisation.

Development of a method for the detection of verotoxin-producing Escherichia coli in food.

The growing recognition of the role of non-O157 verotoxigenic Escherichia coli (VTEC) in foodborne illness underscores the importance of developing methods to detect it in the food supply. We describe here the development of a protocol for the detection, isolation, and characterization of VTEC from foods, designed for the serotype-independent enrichment, detection, and isolation of VTEC, in combination with rapid characterization of VTEC O157, O26, O103, O111, and O145. This study examined the inhibitory concentration of six antimicrobial agents used either singly or in combination for the optimal enrichment of a panel of 18 different O serogroups of VTEC in modified tryptic soy broth. Considerable variability in resistance to the different antimicrobials tested was noted among different VTEC strains. The combination enabling growth of strains of all 18 different O serogroups was vancomycin (10 µg/ml) and cefsulodin (3 µg/ml). A similar combination of antimicrobials formulated in agar plates was found beneficial in the recovery of VTEC strains from enrichment broth cultures. The efficacy of these media in the recovery of selected VTEC (O26, O103, O111, O145, and O157) from ground beef and O157 VTEC from lettuce, spinach, and apple cider was demonstrated. The selective enrichment media described herein would appear suitable for incorporation in methods for the recovery and detection of a wide range of VTEC serogroups.

Myocardial systolic and diastolic consequences of left ventricular mechanical dyssynchrony in heart failure with normal left ventricular ejection fraction.

AIMS: The purpose of this study was to test the hypothesis that left ventricular (LV) mechanical dyssynchrony deteriorates the longitudinal systolic and diastolic function of the left ventricle (LV) in patients with heart failure with a normal LV ejection fraction (HFNEF). METHODS AND RESULTS: In patients with HFNEF and in a control group consisting of asymptomatic patients with LV diastolic dysfunction [LVDD], matched by age, gender, and LV ejection fraction, we assessed the global longitudinal systolic (global strain), diastolic [global early-diastolic strain rate (SRe)], and synchronous (standard deviation of time-to-peak systolic strain) function of the LV by two-dimensional speckle-tracking echocardiography using a 18-segment LV model. A total of 325 patients were included (85 with HFNEF and 240 with asymptomatic LVDD). Patients with HFNEF had a significant impairment of the longitudinal systolic and diastolic function of the LV as compared with the control group. Concerning the pathophysiological mechanisms linked to these findings, we found that HFNEF patients with asynchronous LV contractions had significantly more impaired longitudinal systolic and diastolic LV function (global strain -14.76 ± 3.44%, global SRe 0.79 ± 0.24 s(-1)) than patients without asynchronous LV contractions (global strain -18.57 ± 3.10%, global SRe 1.06 ± 0.32 s(-1); all P < 0.0001). Accordingly, in HFNEF patients with LV mechanical dyssynchrony the rates of LV longitudinal systolic and diastolic dysfunction were 64 and 70%, respectively, whereas these rates were significantly lower (19.5 and 41.3%), respectively, in patients without asynchronous LV contractions. In addition, HFNEF patients with LV mechanical dyssynchrony presented higher LV filling pressures and worse NYHA functional class than those with normal LV contractions. CONCLUSION: In patients with HFNEF, LV mechanical dyssynchrony is associated with an important impairment of the longitudinal systolic and diastolic function of the LV. Therefore, the restoration of asynchronous LV contractions could help to improve and/or correct both the systolic and the diastolic longitudinal dysfunction of the LV in HFNEF and thereby improve the symptomatology of these patients.

Right ventricular myocardial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction.

OBJECTIVE: We hypothesized that in patients with heart failure with normal left ventricular (LV) ejection fraction (HFNEF), the same fibrotic processes that affect the subendocardial layer of the LV could also alter the subendocardial fibers of the right ventricle (RV). Consequently, these alterations and to a lesser extent chronically elevated pulmonary arterial pressures would lead to both systolic and diastolic subendocardial dysfunction of the RV (i.e., impaired RV longitudinal systolic and diastolic function) in patients with HFNEF. METHODS: Patients with HFNEF and a control group consisting of asymptomatic patients with LV diastolic dysfunction (asymptomatic LVDD) matched by age, gender, and LV ejection fraction were studied by two-dimensional speckle-tracking echocardiography. RESULTS: A total of 565 patients were included (201 with HFNEF and 364 with asymptomatic LVDD). RV longitudinal diastolic (RV global longitudinal early-diastolic strain rate [RV-SRe]) and systolic (RV global longitudinal systolic strain [RV-Strain]) function were significantly more impaired in patients with HFNEF than in patients with asymptomatic LVDD (HFNEF: RV-Strain -14.41% ± 3.80% and RV-SRe 0.86 ± 0.33 s(-1); asymptomatic LVDD: RV-Strain -16.90% ± 4.28% and RV-SRe 1.02 ± 0.34 s(-1); all P < .0001). On multiple regression analysis, LV global longitudinal systolic strain was the most important independent predictor of RV longitudinal systolic and diastolic function, in contrast with pulmonary arterial systolic pressure, which was weakly related to these functions. Furthermore, in patients with HFNEF the subendocardial function of both the LV and RV were significantly impaired in similar proportions. In that regard, in patients with HFNEF the prevalences of RV longitudinal systolic and diastolic dysfunction were 75% and 48%, whereas the rates of LV longitudinal systolic and diastolic dysfunction were 80% and 60%, respectively. In addition, patients with both systolic and diastolic longitudinal dysfunction of the RV presented worse New York Heart Association functional class. CONCLUSION: In patients with HFNEF, RV subendocardial systolic and diastolic dysfunction are common and possibly associated with the same fibrotic processes that affect the subendocardial layer of the LV and to a lesser extent with RV pressure overload. Furthermore, our findings suggest that RV longitudinal systolic and diastolic dysfunction could contribute to the symptomatology of patients with HFNEF.

Left atrial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction.

BACKGROUND: The authors hypothesized that in patients with heart failure with normal left ventricular (LV) ejection fraction (HFNEF), the same fibrotic processes that affect the subendocardial layer of the left ventricle could also alter the subendocardial fibers of the left atrium. Consequently, these fibrotic alterations, together with chronically elevated LV filling pressures, would lead to both systolic and diastolic subendocardial dysfunction of the left atrium (i.e., impaired left atrial [LA] longitudinal systolic and diastolic function) in patients with HFNEF. METHODS: Patients with HFNEF and a control group consisting of asymptomatic patients with LV diastolic dysfunction (LVDD) matched by age, gender, and LV ejection fraction were studied using two-dimensional speckle-tracking echocardiography. RESULTS: A total of 420 patients were included (119 with HFNEF and 301 with asymptomatic LVDD). LA longitudinal systolic (LA late diastolic strain rate) and diastolic (LA systolic strain and strain rate) function was significantly more impaired in patients with HFNEF (LA late diastolic strain rate, -1.17 ± 0.63 s(-1); LA systolic strain, 19.9 ± 7.3%; LA systolic strain rate, 1.17 ± 0.46 s(-1)) compared with those with asymptomatic LVDD (-1.80 ± 0.70 s(-1), 30.8 ± 11.4%, and 1.67 ± 0.59 s(-1), respectively) (all P values < .0001). On multiple regression analysis, LV global longitudinal systolic strain and diastolic strain rate were the most important independent predictors of LA longitudinal systolic and diastolic function, in contrast to noninvasive LV filling pressures (i.e., mitral E/e' average septal-lateral ratio), which were modestly related to LA longitudinal systolic and diastolic function. Furthermore, in patients with HFNEF, the subendocardial function of both the left atrium and the left ventricle was significantly impaired in high proportions. In that regard, in patients with HFNEF, the rate of LA longitudinal systolic and diastolic dysfunction was 65.5% and 28.5%, whereas the prevalence of LV longitudinal systolic and diastolic dysfunction was 81.5% and 58%, respectively. In addition, patients with both systolic and diastolic longitudinal dysfunction of the left atrium presented worse NYHA functional class as compared with those with normal LA longitudinal function. CONCLUSIONS: In patients with HFNEF, LA subendocardial systolic and diastolic dysfunction is common and possibly associated with the same fibrotic processes that affect the subendocardial fibers of the left ventricle and to a lesser extent with elevated LV filling pressures. Furthermore, these findings suggest that LA longitudinal systolic and diastolic dysfunction could be related to reduced functional capacity during effort in patients with HFNEF.

A simple PCR-based macroarray system for detection of multiple gene markers in the identification of priority enterohemorrhagic Escherichia coli.

Enterohemorrhagic Escherichia coli (EHEC) strains bearing the O antigenic determinants O157, O26, O111, O103, and O145 have a high rate of association with foodborne illness worldwide. To expand Canadian food inspection capability, a cloth-based hybridization array system (CHAS) was developed for the identification and characterization of priority EHEC. This method targets key virulence genes (eae, hlyA, vt1, and vt2) plus the rfbE gene specifying the O157 antigenic determinant, and the wzx genes specifying the O26, O111, O103, and O145 determinants. Multiplex PCR products incorporating a digoxigenin label were detected by hybridization with an array of specific oligonucleotide probes immobilized on a polyester cloth support, with subsequent immunoenzymatic assay of the captured amplicons. This method identified the relevant markers in 85 different strains bearing various combinations of the target genes (virulence and priority O-antigen markers). None of the target genes was detected in 26 different strains of other E. coli and non-E. coli bacteria. The CHAS demonstrated 100% inclusivity and 100% exclusivity characteristics, with respect to detection of the various markers among different bacterial strains. The CHAS demonstrated 100% inclusivity and 100% exclusivity characteristics, with respect to detection of the markers among various target and nontarget bacteria. The entire procedure could be completed in less than 5 h, and is useful for the identification of priority EHEC colonies isolated from foods by using enrichment culture techniques.

The impact of impaired renal function on mortality in patients with acutely decompensated chronic heart failure.

AIMS: Acute heart failure syndromes, commonly recognized as de novo heart failure or acute decompensated chronic heart failure (ADHF), are characterized by a rapid onset or change in signs and symptoms of heart failure requiring urgent treatment. Coexisting renal dysfunction is associated with poor prognosis in these patients. We sought to determine whether renal impairment in particular and other admission factors in general predict long-term mortality after hospitalization for ADHF. METHODS AND RESULTS: We studied 128 patients (age 63 + or - 12 years, 76% male) in NYHA class 2.6 + or - 0.7 with a left ventricular ejection fraction (LVEF) < or = 39%, hospitalized due to ADHF. Mortality rates (per 100 person-years) were 21.9 at 12 months and 12.0 at 60 months. We found that admission serum creatinine level was the best predictor of mortality after 1 (P < 0.001, log-transformed due to skewed distribution) and 5 years (P = 0.001), followed by creatinine clearance, the use of loop diuretics, and digoxin. Moreover, higher NYHA class, decreased body mass index (BMI) and increased levels of urea predicted 1 and 5 years mortality on univariate analysis. In the multivariate analysis, creatinine, NYHA class, and LVEF emerged as independent predictors of mortality after 1 year, whereas BMI and the use of diuretics did not reach significance (joint chi(2) = 29.40, P < 0.001). After 5 years, creatinine and NYHA class independently predicted all-cause mortality (joint chi(2) = 22.71, P < 0.001), but BMI and age did not remain significant. CONCLUSION: Admission creatinine level strongly predicts medium- and long-term mortality after hospitalization in patients with ADHF, and serves as a cheap and fast clinical marker to identify patients at risk of death.

The relationship between tumor necrosis factor-α, brain natriuretic peptide and atrial natriuretic peptide in patients with chronic heart failure.

BACKGROUND: Cytokines such as tumor necrosis factor-alpha (TNF) contribute to cardiac dysfunction in chronic heart failure (CHF). Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are thought to reflect cardiac functional and structural damage. METHODS AND RESULTS: To study the relationship between BNP, ANP, and TNF, these parameters were measured in fasting venous blood samples of 25 CHF patients (age 66+/-2 years, pVO(2) 17.4+/-2.1 mL/kg/min, NYHA class 2.8+/-0.2, all mean+/-SEM) and 8 healthy controls (age 71+/-2 years). Patients with CHF had higher plasma levels of BNP (p<0.05), ANP (p<0.05), norepinephrine (p<0.01), and echocardiographic left ventricular end-diastolic diameter (LVEDD, p<0.05) compared to controls, whereas TNF and epinephrine were not significantly different. There were significant correlations between natriuretic peptides and markers of inflammation and myocardial dysfunction in CHF patients: BNP vs. TNF (r=0.64, p=0.0006), vs. LVEDD (r=0.59, p=0.0025); ANP vs. TNF (r=0.60, p=0.0016), vs. LVEDD (r=0.65, p=0.0006); TNF vs. LVEDD (r=0.57, p=0.004). After adjustment for NYHA, creatinine clearance, and age TNF correlated with BNP (all p=0.01) and ANP (all p<0.002). The cachectic CHF patients (n=7,>6% weight loss) had the highest BNP (p<0.001 vs. controls, p<0.05 vs. non-cachectic CHF) and ANP levels (p=0.01 vs. controls). Concentrations of uric acid, epinephrine, and norepinephrine also correlated with ANP and BNP. CONCLUSION: In CHF, TNF is closely related to BNP and ANP (independently of CHF severity and ventricular dysfunction), particularly in patients with cardiac cachexia. TNF may causally contribute to intrinsic cardiac dysfunction thereby stimulating BNP and ANP secretion.

Development of unique bacterial strains for use as positive controls in the food microbiology testing laboratory.

Nalidixic acid-resistant (NalR) mutants of Salmonella enterica serovar Berta and Escherichia coli O157:H7 were derived from wild-type laboratory cultures to serve as distinguishable control strains for routine use in food microbiology testing programs. The prevalence of the NalR phenotype among different bacteria was verified using panels of related and unrelated strains with the ability to grow vigorously on plating media containing nalidixic acid, being restricted to the NalR mutants. The NalR phenotype was stable in both mutant strains over several generations in the absence of selective pressure and enabled their differentiation from wild-type bacteria on the basis of their ability to grow on plating media containing nalidixic acid. A similar approach for the development of a distinguishable Listeria monocytogenes control strain was not possible due to the inherent resistance of this organism to nalidixic acid. Instead, an L. monocytogenes isolate with rare genotypic and serologic features was identified as a possible candidate to serve as a unique and distinguishable positive control strain.

Rapid discrimination of Salmonella isolates by single-strand conformation polymorphism analysis.

A molecular typing technique was developed for the differentiation of Salmonella isolates based on single-strand conformation polymorphism (SSCP) analysis of amplicons generated by PCR. Amplicons from parts of the fimA (both the 5' and 3' ends), mdh, invA, and atpD genes were generated separately from a panel of Salmonella strains representing Salmonella bongori, and four subspecies and 17 serovars of Salmonella enterica. These amplicons were subjected to SSCP analysis for differentiation of the salmonellae on the basis of different conformational forms arising due to nucleotide sequence variations in the target genes. Several distinct SSCP banding patterns (a maximum of 14 each for atpD and fimA 3' end) were observed with this panel of Salmonella strains for amplicons generated from each target gene. The best discrimination of Salmonella subspecies and serovar was achieved from the SSCP analysis of a combination of at least three gene targets: atpD, invA, and either mdh or fimA 3' end. This demonstrates the applicability of SSCP analysis as an important additional method to classical typing approaches for the differentiation of foodborne Salmonella isolates. SSCP is simple to perform and should be readily transferable to food microbiology laboratories with basic PCR capability.

Detection of group D salmonellae including Salmonella Enteritidis in eggs by polymyxin-based enzyme-linked immunosorbent assay.

A high-throughput, rapid method was devised for the detection of Salmonella Enteritidis in egg products. For each target organism, preenrichment in nutrient broth was followed by selective enrichment in Rappaport-Vassiliadis soya peptone and tetrathionate brilliant green broths or by plating on modified semisolid Rappaport Vassiliadis (MSRV) agar medium. The presence of Salmonella Enteritidis was determined by subjecting portions of the selective broth cultures or swarming growth on MSRV medium to an enzyme-linked immunosorbent assay (ELISA) procedure using polymyxin immobilized in the wells of a microtiter plate as a high-affinity adsorbent for lipopolysaccharide (LPS) antigens. Sample extracts were reacted with polymyxin-coated microwells, and captured LPS antigens were detected immunoenzymatically with a commercially available Salmonella factor O9-specific antibody. The polymyxin-ELISA was 100% sensitive and 100% specific for Salmonella strains bearing the O9 antigen. When the ELISA was combined with enrichment using either the selective broths or plating on MSRV medium, the system was an effective means for detection of Salmonella Enteritidis in artificially inoculated egg products. The polymyxin-ELISA is a simple and inexpensive assay for group D salmonellae (including Salmonella Enteritidis) in a convenient 96-well microtiter plate format, making this system ideally suited for processing large numbers of samples.