Identification and characterization of a new soybean promoter induced by Phakopsora pachyrhizi, the causal agent of Asian soybean rust.

BACKGROUND: Phakopsora pachyrhizi is a biotrophic fungal pathogen responsible for the Asian soybean rust disease causing important yield losses in tropical and subtropical soybean-producing countries. P. pachyrhizi triggers important transcriptional changes in soybean plants during infection, with several hundreds of genes being either up- or downregulated. RESULTS: Based on published transcriptomic data, we identified a predicted chitinase gene, referred to as GmCHIT1, that was upregulated in the first hours of infection. We first confirmed this early induction and showed that this gene was expressed as early as 8 h after P. pachyrhizi inoculation. To investigate the promoter of GmCHIT1, transgenic soybean plants expressing the green fluorescence protein (GFP) under the control of the GmCHIT1 promoter were generated. Following inoculation of these transgenic plants with P. pachyrhizi, GFP fluorescence was detected in a limited area located around appressoria, the fungal penetration structures. Fluorescence was also observed after mechanical wounding whereas no variation in fluorescence of pGmCHIT1:GFP transgenic plants was detected after a treatment with an ethylene precursor or a methyl jasmonate analogue. CONCLUSION: We identified a soybean chitinase promoter exhibiting an early induction by P. pachyrhizi located in the first infected soybean leaf cells. Our results on the induction of GmCHIT1 promoter by P. pachyrhizi contribute to the identification of a new pathogen inducible promoter in soybean and beyond to the development of a strategy for the Asian soybean rust disease control using biotechnological approaches.

Cranioplasty with bandaging. New forms of limitation of life support and organ donation.

Most of transplanted organs are obtained from brain death (BD) donors. In neurocritical patients with catastrophic injuries and decompressive craniectomy (DC), which show a dreadful development in spite of this treatment, DC could be a futile tool to avoid natural progress to BD. We propose if cranial compressive bandage (cranioplasty with bandage) could be an ethically correct practice, similar to other life-sustaining treatment limitation (LSTL) common methods. Based on a clinical case, we contacted with the Assistance Ethics Committee and some bioethics professionals asking them two questions: 1) Is ethically correct to perform a cranioplasty with bandage in those patients with LSTL indication? 2) Thinking in organ donation possibility, is this option preferable? Conclusions 1) Cranioplasty with bandage could be considered an ethically acceptable LSTL practice, similar to other procedures. 2) It facilitates organ donation for transplant, which provides value-added because of its own social good. 3) In these cases, it is necessary to know previous patient's will or, in absentia, to obtain family consent after a detailed procedure report.

[Ethical recommendations for a difficult decision-making in intensive care units due to the exceptional situation of crisis by the COVID-19 pandemia: A rapid review & consensus of experts]. / Recomendaciones éticas para la toma de decisiones difíciles en las unidades de cuidados intensivos ante la situación excepcional de crisis por la pandemia por COVID-19: revisión rápida y consenso de expertos.

In view of the exceptional public health situation caused by the COVID-19 pandemic, a consensus work has been promoted from the ethics group of the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC), with the objective of finding some answers from ethics to the crossroads between the increase of people with intensive care needs and the effective availability of means.In a very short period, the medical practice framework has been changed to a 'catastrophe medicine' scenario, with the consequent change in the decision-making parameters. In this context, the allocation of resources or the prioritization of treatment become crucial elements, and it is important to have an ethical reference framework to be able to make the necessary clinical decisions. For this, a process of narrative review of the evidence has been carried out, followed by a unsystematic consensus of experts, which has resulted in both the publication of a position paper and recommendations from SEMICYUC itself, and the consensus between 18 scientific societies and 5 institutes/chairs of bioethics and palliative care of a framework document of reference for general ethical recommendations in this context of crisis.

Validation of the Spanish version of the liver disease quality of life instrument among candidates for liver transplant.

OBJECTIVE: To validate a Spanish version of the Liver Disease Quality of Life Questionnaire (LDQOL 1.0) among patients awaiting hepatic transplantation. METHODS: This observational, cross-sectional study was performed between May 2002 and June 2006. We included ambulatory or hospitalized patients aged 18 or over with chronic liver disease awaiting transplantation. Patients completed the LDQOL 1.0. The feasibility of the LDQOL for clinical use was tested by examining the administration time and values for the questionnaire's 12 disease-specific scales. Reliability was tested by examining the internal consistency of the scales (Cronbach's alpha). Known group validity was tested by examining the questionnaire's ability to discriminate between patients with hepatocellular (HCC), liver cirrhosis (CH), hepatitis C virus infection, and alcohol-induced CH. RESULTS: A total of 200 patients were included in the analysis. Their mean age (SD) was 52.6 (9.8) years; 73% of the sample were men. The most common indication for liver transplant was HCC (34%). The mean (SD) time to complete the LDQOL 1.0 was 35 minutes (21 minutes). Over 20% of patients scored at the ceiling (maximum possible score) on seven of the 12 disease-specific scales. Floor effects were less marked. All dimensions had Cronbach alpha coefficients over 0.60. The lowest value (0.64) was found in the sexual problems (women) dimension. Patients with HCC had significantly higher scores on several scales, including symptoms of liver disease (P = .000), effects of liver disease (P = .000), concentration (P = .002), memory (P = .015), quality of social interaction (P = .030), sleep (P = .000), loneliness (P = .043), and stigma (P = .028). Statistically significant differences were found between HCC patients and alcohol-induced CH patients in only two dimensions. CONCLUSIONS: Among pretransplant patients, the Spanish version of the LDQOL 1.0 showed substantial ceiling effects and the length of administration makes its application in clinical practice difficult. This preliminary analysis showed good internal consistency for the disease-specific scales and acceptable known group validity.

Multicenter study of the multiple organ dysfunction syndrome in intensive care units: the usefulness of Sequential Organ Failure Assessment scores in decision making.

OBJECTIVE: This study examined the incidence and mortality of multiple organ dysfunction syndrome (MODS) in intensive care units, evaluated the limitation of life support in these patients, and determined whether daily measurement of the Sequential Organ Failure Assessment (SOFA) is useful for decision making. DESIGN AND SETTING: Prospective, observational study in 79 intensive care units. PATIENTS AND PARTICIPANTS: Of the 7,615 patients admitted during a 2-month period we found 1,340 patients to have MODS. MEASUREMENTS AND RESULTS: We recorded mortality and length of stay in the intensive care unit and the hospital and the maximum and minimum total SOFA scores during MODS. Limitation of life support in MODS patients was also evaluated. Stepwise logistic regression was used to determine the factors predicting mortality. The in-hospital mortality rate in patients with MODS was 44.6%, and some type of limitation of life support was applied in 70.6% of the patients who died. The predictive model maximizing specificity included the following variables: maximum SOFA score, minimum SOFA score, trend of the SOFA for 5 consecutive days, and age over 60 years. The model diagnostic yield was: specificity 100%, sensitivity 7.2%, positive predictive value 100%, and negative predictive value 57.3%; the area under the receiver operating characteristic curve was 0.807. CONCLUSIONS: This model showed that in our population with MODS those older than 60 years and with SOFA score higher than 9 for at least 5 days were unlikely to survive.

Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost-benefit analysis.

The purpose of this study was to evaluate and compare the clinical effects, safety, and economic cost of propofol and midazolam in the sedation of patients undergoing mechanical ventilation in the ICU. Eighty-eight critically ill patients were studied and randomly allocated to receive short-term (less than 24 h), medium-term (24 h to 7 days), and prolonged (more than 7 days) continuous sedation with propofol (n = 46) or midazolam (n = 42). Mean doses required were 2.36 mg/kg/h for propofol and 0.17 mg/kg/h for midazolam. Patients in the group receiving propofol showed a percentage of hours of sedation at the desired level (grade 2, 3, 4, or 5 on the Ramsay scale) of 93 percent, compared with 82 percent (p < 0.05) in the group receiving midazolam. Both agents were considered safe with respect to the induction of adverse reactions during their use in prolonged sedation. Recovery after interrupting sedation was significantly faster in patients treated with propofol than in those sedated with midazolam (p < 0.05). Recovery of total consciousness was predictable according to sedation time in propofol-treated subgroups (r = 0.98, 0.88, and 0.92, respectively), while this correlation was not observed in the midazolam-treated group. In the subgroup with sedation of less than 24 h, propofol provided a cost savings of approximately 2,000 pesetas (pts) per patient, due to shorter stays in the ICU. We conclude that propofol is a sedative agent with the same safety, higher clinical effectiveness, and a better cost-benefit ratio than midazolam in the continuous sedation of critically ill patients.

Freud-Ferenczi: controversy terminable and interminable.

Following Balint's view that the psychoanalytic community was traumatised by the Freud-Ferenczi controversy, the author considers whether the roots of the confrontation between drive-based and object-relations theories might lie in a failure to examine this disagreement in sufficient depth. Increasing interest, as reflected in the literature, is now focusing on Ferenczi's ideas after many years of neglect due in part to Jones's 'official' account of the 'mental deterioration' of his last years. Adducing late works by both Freud and Ferenczi, the author shows that the latter amplified Freud's ideas rather than breaking with them. To Freud, who had always been concerned to stress the role of the drives in psychopathology, Ferenczi's emphasis on external trauma smacked of his own, rejected, early seduction theory, but trauma does feature prominently in Freud's discussion of interminable analyses, as does Ferenczi himself. In the author's view, a careful reading of the two men's late works reveals a conception of trauma as lying in an intersubjective space as a consequence of the meeting of drive and object. Present-day conceptions of transgenerational trauma are shown to be already present in Ferenczi. The problems in the relationship between Freud and Ferenczi and their theoretical disagreements are also considered in the light of the latter's inadequate analysis with Freud.

[Ethics of the cardiopulmonary resuscitation decisions]. / Ética de las decisiones en resucitación cardiopulmonar.

Cardiopulmonary Resuscitation (CPR) must be attempted if indicated, not done if it is not indicated or if the patient does not accept or has previously rejected it and withdrawn it if it is ineffective. If CPR is considered futile, a Do-Not-Resuscitate Order (DNR) will be recorded. This should be made known to all physicians and nurses involved in patient care. It may be appropriate to limit life-sustaining-treatments for patients with severe anoxic encephalopathy, if the possibility of clinical evolution to brain death is ruled out. After CPR it is necessary to inform and support families and then review the process in order to make future improvements. After limitation of vital support, certain type of non-heart-beating-organ donation can be proposed. In order to acquire CPR skills, it is necessary to practice with simulators and, sometimes, with recently deceased, always with the consent of the family. Research on CPR is essential and must be conducted according to ethical rules and legal frameworks.

[Cost of quality in Intensive Medicine. Guidelines for clinical management]. / Costes de la calidad en Medicina Intensiva. Guía para gestores clínicos.

OBJECTIVE: This article reviews the utility and applicability of available systems in order to calculate general and quality costs in clinical services settings. METHODS: Review of techniques to calculate costs in Intensive Care Units (ICUs) according to analytical accounting approaches. RESULTS: The methodological development is complemented with the results of its application in the ICU of the Miracle's Hospital showing the structure of costs and the results obtained with this methodology when analyzing the costs of activities related to quality improvement. CONCLUSIONS: The effort to implement systems focused to analyze general and quality costs will result in a benefit of those participating in the healthcare system: citizens, professionals, managers, and "financials" since that which is only a legitimate demand today will be a inexcuseable commitment of the healthcare professionals from the society tomorrow.

Cost of ICU sedation: comparison of empirical and controlled sedation methods.

A randomised crossover study was undertaken to compare the quality and cost of controlled versus empirical sedation with midazolam in critically ill patients. Patients (n = 40) entering the ICU were enrolled provided they satisfied the strict entry criteria. During 90 hours of midazolam sedation, patients received randomly allocated 10-hour periods of controlled or empirical sedation. With empirical sedation, the mean dose of midazolam and the cost of sedation were almost double those with controlled sedation. The quality of sedation was superior with the controlled method. In a separate study on 352 patients, a cost-benefit analysis of controlled sedation with midazolam or propofol infusion or bolus injections of morphine plus diazepam showed that the quality of sedation achieved with propofol was superior to the other two regimens and that, with morphine plus diazepam, the quality of sedation was unacceptably poor. Although the direct purchase price of propofol was higher than that of other agents, the total cost of sedation with propofol was lower than that for midazolam for short-term intensive care (less than 24 hours) and comparable to midazolam for longer-term use. However, indirect benefits of sedation with propofol include a much shorter ICU stay with the attendant reduced nursing costs and greater throughout the patients, and this more than compensates for the higher purchase price of the agent.

Synergistic sedation with propofol and midazolam in intensive care patients after coronary artery bypass grafting.

OBJECTIVES: To evaluate and compare the clinical efficacy, impact on hemodynamics, safety profiles, and cost of combined administration of propofol and midazolam (synergistic sedation) vs. midazolam and propofol administered as sole agents, for sedation of mechanically ventilated patients after coronary artery bypass grafting. DESIGN: Prospective, controlled, randomized, double-blind clinical trial. SETTING: Intensive care unit of SCIAS-Hospital de Barcelona. PATIENTS: Seventy-five mechanically ventilated patients who underwent coronary artery bypass graft surgery under low-dose opioid anesthesia. INTERVENTIONS: According to the double-blind method, patients were randomly assigned to receive propofol (n = 25), midazolam (n = 25), or propofol combined with midazolam (n = 25). Infusion rates were adjusted to stay between 8 and 11 points on Glasgow Coma Score modified by Cook and Palma. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD duration of sedation was 14.4 +/- 1.5 hrs, 14.1 +/- 1.1 hrs, and 14.7 +/- 1.9 hrs for the propofol, midazolam, and synergistic groups, respectively. The induction dose was 0.55 +/- 0.05 mg/kg for propofol as sole agent, 0.05 +/- 0.01 mg/kg for midazolam as sole agent, and 0.22 +/- 0.03 mg/kg for propofol administered in combination with 0.02 +/- 0.00 mg/kg of midazolam (p = .001). The maintenance dose was 1.20 +/- 0.03 mg/kg/hr for propofol as sole agent, 0.08 +/- 0.01 mg/kg/hr for midazolam as sole agent, and 0.50 +/- 0.09 mg/kg/hr for propofol administered in combination with 0.03 +/- 0.01 mg/kg/hr of midazolam (p < .001). All sedative regimens achieved similar efficacy in percentage of hours of adequate sedation (93% for propofol, 88% for midazolam, and 90% for the synergistic group, respectively). After induction, both propofol and midazolam groups had significant decreases in systolic blood pressure, diastolic blood pressure, left atrial pressure, and heart rate. Patients in the synergistic group had significant bradycardia throughout the study, without impairment in other hemodynamic parameters. Patients sedated with propofol or synergistic regimen awoke sooner and could be extubated before those patients sedated with midazolam (0.9 +/- 0.3 hrs and 1.2 +/- 0.6 hrs vs. 2.3 +/- 0.8 hrs, respectively, p = .01). Synergistic sedation produced cost savings of 28% with respect to midazolam and 68% with respect to propofol. CONCLUSIONS: In the study conditions, the new synergistic treatment with propofol and midazolam administered together is an effective and safe alternative for sedation, with some advantages over the conventional regimen with propofol or midazolam administered as sole agents, such as absence of hemodynamic impairment, >68% reduction in maintenance dose, and lower pharmaceutical cost.

Inadvertent gonadotrophin-releasing hormone agonist (GnRHa) administration in the luteal phase may improve fecundity in in-vitro fertilization patients.

Spontaneous pregnancies associated with inadvertent periconceptional administration of a gonadotrophin-releasing hormone agonist (GnRHa) occur in approximately 1% of in-vitro fertilization (IVF) cycles. The two main issues to be considered in these circumstances are the luteolytic effect of the agonist and embryotoxicity. In addition, some authors have suggested a higher incidence of ectopic implantations. In view of these concerns, we report on 15 patients who conceived during pituitary desensitization with a GnRHa in the luteal phase of the menstrual cycle, and review the literature on the subject. A detailed analysis of the data available so far, which include 59 pregnancies exposed to GnRHa, shows that: (i) there is no clinical evidence for impaired luteal function, and hormonal supplementation does not improve pregnancy outcome; (ii) with only two cases of reported minor malformations among 37 deliveries, both having a genetic component, there is no evidence of teratogenic effects; and (iii) ectopic implantations in these circumstances are related to tubal disease but not to the drug. Considering the long history of infertility in these patients who had previously been treated unsuccessfully by different therapeutic modalities, it is likely that the occurrence of those pregnancies is not merely coincidental and that GnRHa might have a positive role in fecundity. The improved fecundity may be explained by the mechanisms of luteinizing hormone action in the corpus luteum.

Efficacy and safety of two new methods of rapid intravenous detoxification in heroin addicts previously treated without success.

BACKGROUND: New methods of rapid opiate detoxification, under intravenous sedation, can detoxify heroin-addicted patients in 24 hours. Their clinical application has been limited by the lack of studies establishing both efficacy and safety. METHOD: In a randomised, controlled study, 300 treatment-refractory, heroin-addicted patients received rapid intravenous detoxification treatment (naloxone infusion, 0.06-0.08 mg/kg, then oral naltrexone 50 mg/day) under either monitored light intravenous sedation or unmonitored deep intravenous sedation. RESULTS: All patients were successfully detoxified and 93% remained abstinent one month later. Severity of withdrawal, according to the Wang Scale modified by Loimer, was 4.9 (s.d. 3.0) points in the light sedation group and 4.8 (s.d. 2.9) in the deep sedation group (P = 0.26). Two patients (1.3%) in the light sedation group and four (2.6%) in the deep sedation group required tracheal intubation (P = 0.31). There was only one severe complication, a case of nosocomial aspirative pneumonia which improved with antibiotic treatment. CONCLUSIONS: Successful rapid intravenous detoxification can be achieved using relatively light levels of sedation.