The balance between fitness advantages and costs drives adaptation of bacteriophage Qß to changes in host density at different temperatures.

Introduction: Host density is one of the main factors affecting the infective capacity of viruses. When host density is low, it is more difficult for the virus to find a susceptible cell, which increases its probability of being damaged by the physicochemical agents of the environment. Nevertheless, viruses can adapt to variations in host density through different strategies that depend on the particular characteristics of the life cycle of each virus. In a previous work, using the bacteriophage Qß as an experimental model, we found that when bacterial density was lower than optimal the virus increased its capacity to penetrate into the bacteria through a mutation in the minor capsid protein (A1) that is not described to interact with the cell receptor. Results: Here we show that the adaptive pathway followed by Qß in the face of similar variations in host density depends on environmental temperature. When the value for this parameter is lower than optimal (30°C), the mutation selected is the same as at the optimal temperature (37°C). However, when temperature increases to 43°C, the mutation selected is located in a different protein (A2), which is involved both in the interaction with the cell receptor and in the process of viral progeny release. The new mutation increases the entry of the phage into the bacteria at the three temperatures assayed. However, it also considerably increases the latent period at 30 and 37°C, which is probably the reason why it is not selected at these temperatures. Conclusion: The conclusion is that the adaptive strategies followed by bacteriophage Qß, and probably other viruses, in the face of variations in host density depend not only on their advantages at this selective pressure, but also on the fitness costs that particular mutations may present in function of the rest of environmental parameters that influence viral replication and stability.

Endocrine Evaluation and Homeostatic Model Assessment in Patients with Cornelia de Lange Syndrome.

Objective: The aim of this study was to expand knowledge about endocrine disorders in individuals with Cornelia de Lange syndrome (CdLS), a rare developmental genetic disorder with anomalies in multiple organs and systems. Methods: Hormone levels, clinical scores, anthropometric measurements, and molecular analysis were assessed in 24 individuals with CdLS. Results: Hyperprolactinemia was the most common endocrine disorder. Three patients showed subclinical hypothyroidism. In the gonadotropic axis, mildly delayed puberty was observed, as well as genital anomalies, such as cryptorchidism. Despite short stature, levels of insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 were normal, on average. Three prepubertal individuals without risk factors had higher than normal values for the homeostatic model assessment of insulin resistance (HOMA-IR) and for insulinemia, suggesting insulin resistance. Furthermore, two adults had elevated BMIs associated with HOMA-IR values over the cut-off values. Conclusion: CdLS can lead to dysregulation of the endocrine system, particularly in patients with high HOMA-IR values and insulinemia who are at risk of insulin resistance. Therefore, clinical follow-ups with hormonal assessments are proposed for individuals with CdLS.

Prevalence and mortality of patients with palliative needs in an acute respiratory setting / Prevalencia y mortalidad de pacientes con necesidades paliativas en una planta de Neumología. Estudio prospectivo

Introduction: NECPAL is a tool for identification of patients with advanced chronic disease in need of palliative care. The main objective of the study is to know the prevalence of patients with palliative needs in an acute respiratory ward in a Spanish tertiary hospital using NECPAL. A second objective of the study is to know the annual mortality rate of these patients.Materials and methods: Cross sectional study and prospective monitoring of a cohort identified as palliative patients with the NECPAL tool for 12 months. Patient identification was performed in patients admitted to the respiratory ward of our hospital for longer than 3 days. We have assessed the annual vital status (deceased or not deceased) of patients and have recorded demographics, clinical and functional data, as well as the use of healthcare resources.Results: We monitored a cohort of 363 patients. Of them, 87 patients (24.3%) (IC 95% 19–30) were identified as NECPAL positive. 60% of patients (n = 64) died within 12 months of their admission. There was no significant difference in the mortality ratio of oncologic versus non oncologic patients. In a multivariable analysis, mortality was associated with demand by patients or relatives for palliative care and with the presence of specific disease progression markers or indicators.Conclusions: prevalence of patients with palliative needs in acute respiratory wards is high (one out of four patients). 60% of the patients identified as NECPAL positive in our cohort died in the first 12 months. Training of healthcare professionals as well as availability of appropriate resources are indispensable factors to improve care of this population. (AU)

Introducción: El instrumento NECPAL es una herramienta para la identificación de personas en situación de enfermedad crónica avanzada con necesidades paliativas. El objetivo del estudio es conocer la prevalencia de pacientes con necesidades paliativas en un Servicio de Neumología de un hospital terciario mediante la herramienta NECPAL. Como objetivo secundario se plantea conocer la mortalidad al año de estos pacientes.Material y métodos: Estudio trasversal y seguimiento prospectivo de la cohorte de los pacientes identificados como paliativos con la herramienta NECPAL durante 12 meses. La identificación se realiza en pacientes ingresados > 3 días en una planta de Neumología. Hemos evaluado el estatus vital (fallecido o no fallecido) al año, así como datos demográficos clínicos, funcionales y uso de recursos sanitarios.Resultados: Se analizaron 363 pacientes. De ellos, 87 (24,3%) (IC 95%, 19–30) fueron identificados como NECPAL positivos. En el seguimiento durante un año fallecieron 54 pacientes, un 60%. No hubo diferencias en mortalidad entre diagnósticos oncológicos y no oncológicos. En el análisis multivariante, la mortalidad se asoció a la demanda de paciente o familiares de atención paliativa y a la presencia de indicadores específicos de progresión de la enfermedad.Conclusiones: La prevalencia de pacientes con necesidades paliativas en una planta de hospitalización de agudos de Neumología es alta (uno de cada cuatro pacientes). El 60% de los identificados como NECPAL positivos en nuestra serie fallece en los primeros 12 meses. Son necesarios formación y recursos para atender a estos pacientes. (AU)

Prevalence and Mortality of Patients with Palliative Needs in an Acute Respiratory Setting. / Prevalencia y mortalidad de pacientes con necesidades paliativas en una planta de Neumología. Estudio prospectivo.

INTRODUCTION: NECPAL is a tool for identification of patients with advanced chronic disease in need of palliative care. The main objective of the study is to know the prevalence of patients with palliative needs in an acute respiratory ward in a Spanish tertiary hospital using NECPAL. A second objective of the study is to know the annual mortality rate of these patients. MATERIALS AND METHODS: Cross sectional study and prospective monitoring of a cohort identified as palliative patients with the NECPAL tool for 12 months. Patient identification was performed in patients admitted to the respiratory ward of our hospital for longer than 3 days. We have assessed the annual vital status (deceased or not deceased) of patients and have recorded demographics, clinical and functional data, as well as the use of healthcare resources. RESULTS: We monitored a cohort of 363 patients. Of them, 87 patients (24.3%) (IC 95% 19-30) were identified as NECPAL positive. 60% of patients (n = 64) died within 12 months of their admission. There was no significant difference in the mortality ratio of oncologic versus non oncologic patients. In a multivariable analysis, mortality was associated with demand by patients or relatives for palliative care and with the presence of specific disease progression markers or indicators. CONCLUSIONS: prevalence of patients with palliative needs in acute respiratory wards is high (one out of four patients). 60% of the patients identified as NECPAL positive in our cohort died in the first 12 months. Training of healthcare professionals as well as availability of appropriate resources are indispensable factors to improve care of this population.

Amanitinas / Amanitines

La intoxicación por consumo de hongos es un fenómeno estacional que se produce con relativa frecuencia en áreas geográficas donde es habitual su consumo, en especial de especies silvestres. Dependiendo del tipo de hongo ingerido pueden aparecer distintos cuadros clínicos (gastrointestinal, nefrotóxico, alucinatorio, etc.). El cuadro más grave es el hepatotóxico, asociado a una alta mortalidad, y causado por hongos que contienen amatoxinas (síndrome ciclopeptídico). Presentamos una revisión actualizada de las características de las amatoxinas, su cinética y mecanismo de acción, los métodos utilizados para su determinación analítica, así como las diferentes opciones para el tratamiento de la intoxicación (AU)

Mushroom poisoning is a seasonal phenomenon that occurs relatively frequently in geographical areas where its consumption is common. Depending on the type of fungus ingested different clinical symptoms (gastrointestinal, nephrotoxic, hallucinatory, etc.) can occur. Hepatotoxic syndrome caused by fungi containing amatoxins is the most serious condition, associated to high mortality. We present an updated review of amatoxins characteristics, kinetics, mechanism of action, methods used for analytical determination, as well as the different options for the treatment of poisoning (AU)

Desoxipipradrol. Fármacos antiguos, problemas nuevos / Desoxypipradrol. Old drugs, new problems

A través de Internet recientemente se han comercializado algunas sustancias estimulantes estructuralmente parecidas a neurotransmisores derivadas de medicamentos ya retirados, que potencialmente pueden causar cuadros clínicos de diversa gravedad. Su efecto estimulante y el hecho de que aparecen antes de prohibirse su consumo explican la denominación genérica de legal highs. La exposición a estas sustancias se manifiesta como cuadros parecidos a los del consumo de productos como fenciclidina, anfetaminas o cocaína, ya que muy probablemente compartan mecanismos de acción sobre la recaptación de dopamina en los núcleos cerebrales implicados en el comportamiento de gratificación. La escasez de información médica contrastada, y las dificultades para disponer de material de calibración constituyen un reto diagnóstico. El desoxipipradol, sintetizado hace más de 6 décadas para el tratamiento del trastorno hipercinético, fue relegado por el metilfenidato, un compuesto análogo. En 2009 reapareció como droga recreativa responsable de algunos cuadros clínicos de intoxicación (AU)

Stimulant substances previously used for therapeutic purposes, and are currently banned, have recently been marketed through the Internet. These drugs, structurally similar to neurotransmitters, can potentially cause severe clinical conditions. Exposure to these 'legal highs' results in symptoms similar to those of well-known substances such as phencyclidine, amphetamines or cocaine, probably because they share mechanisms of action related to dopamine reuptake in brain nuclei involved in the regulation of reward behavior. The limitations of medical evidence, as well as difficulties in obtaining calibration material, constitute an analytical challenge. Desoxypipradol was synthesized more than six decades ago for the treatment of hyperkinetic disorder, but was surpassed by methylphenidate, a similar compound with a better pharmacokinetic performance. In 2009 desoxypipradol appeared as a recreational drug involved in several cases of clinical intoxication (AU)

Plasma procalcitonin measured by time-resolved amplified cryptate emission (TRACE) in liver transplant patients. A prognosis marker of early infectious and non-infectious postoperative complications.

BACKGROUND: Elevated procalcitonin (PCT) levels are observed after major surgery, such as orthotopic liver transplantation (OLTx). The aim of this observational study was to evaluate PCT kinetics during the first 5 following days after surgery to establish the prognostic value of PCT changes in the outcome of OLTx, and to predict medical, technical and infectious complications. PCT was also evaluated in the differential diagnosis of infection vs. rejection. METHODS: A total of 64 OLTx were performed in 58 patients; they were split into two groups: with and without complications. Out of these patients, 18 developed infection, and nine rejection. PCT was measured before and during surgery, 12 h after transplantation and daily for the 5 following days. PCT was also measured the day when infection or rejection was diagnosed, and on the previous day. PCT was determined by time-resolved amplified cryptate emission (TRACE) technology. RESULTS: PCT elevation began at 12 h after surgery, reaching a peak on the 1st day in both groups. Significantly higher PCT concentrations were found in the group of patients developing complications, on the 5 postoperative days. It was found that a 24 h PCT value higher than 1.92 microg/L increased by 9.1-time-fold the risk of complications. When infection was diagnosed, a second peak of PCT was observed, but no PCT elevation was shown in rejection. CONCLUSIONS: Daily monitored PCT provides valuable information about the early outcome of OLTx.

Umbilical cord blood serum procalcitonin by Time-Resolved Amplified Cryptate Emission (TRACE) technology: reference values of a potential marker of vertically transmitted neonatal sepsis.

BACKGROUND: Neonatal infection remains a major diagnostic problem because of non-specific clinical signs and symptoms, as well as low sensitivity and specificity of routine laboratory tests. C-reactive protein (CRP), white blood cell count, absolute neutrophil count and immature/total neutrophil ratio are the most widely used tests in the diagnosis of sepsis and provide useful information, but none of these has demonstrated to be reliable in detecting all septic infants. Procalcitonin (PCT) has been suggested as a potentially useful laboratory test performed in umbilical cord blood when perinatal bacterial sepsis is under investigation. METHODS: In this study, the reference interval for umbilical cord blood serum PCT was established for the first time by Time-Resolved Amplified Cryptate Emission (TRACE) technology. RESULTS: The reference interval for PCT in umbilical cord blood serum ranged from 0.04 to 0.43 microg/L in 168 non-infected newborn infants (95% CI 0.02-0.06 and 0.35-0.60 microg/L, respectively). Cord blood serum PCT correctly classified one infected patient out of 90 newborn infants at risk of vertically transmitted sepsis and identified another neonate as a potentially infected patient despite having negative blood cultures. However, cord blood CRP misclassified 21 out of the 90 patients as infected neonates. CONCLUSIONS: Cord blood PCT measured by TRACE is a potentially more useful early marker of neonatal sepsis than cord blood CRP.