Factors associated with unjustified chronic treatment with digoxin in patients with acute heart failure and relationship with short-term prognosis.

OBJECTIVES: To analyze the factors related to inadequate chronic treatment with digoxin and whether the inadequacy of treatment has an impact on short-term outcome. METHOD: Patients diagnosed with AHF who were in chronic treatment with digoxin, were selected. Digoxin treatment was classified as adequate or inadequate. We investigated factors associated to inadequacy and whether such inadequacy was associated with in-hospital and 30-day mortality, prolonged hospital stay (>7 days) and combined adverse event (re-consultation to the ED or hospitalization for AHF or death from any cause) during the 30 days after discharge. RESULTS: We analyzed 2,366 patients on chronic digoxin treatment (median age = 83 years, women = 61%), which was considered adequate in 1,373 cases (58.0%) and inadequate in 993 (42.0%). The inadequacy was associated with older age, less comorbidity, less treatment with beta-blockers and renin-angiotensin inhibitors, better ventricular function, and worse Barthel index. In-hospital and 30-day mortality was higher in patients with inadequate digoxin treatment (9.9% versus 7.6%, p = 0.05; and 12.6% versus 9.1%, p < 0.001, respectively). No differences were recorded in prolonged stay (35.7% versus 33.8%) or post-discharge adverse events (32.9% versus 31.8%). In the model adjusted for baseline and decompensation episode differences, inadequate treatment with digoxin was not significantly associated with any outcome, with an odds ratio of 1.31 (95%CI = 0.85-2.03) for in-hospital mortality; 1.29 (0.74-2.25) for 30-day mortality; 1.07 (0.82-1.40) for prolonged stay; and 0.88 (0.65-1.19) for post-discharge adverse event. CONCLUSION: There is a profile of patients with AHF who inadequately receive digoxin, although this inadequateness for chronic digitalis treatment was not associated with short-term adverse outcomes.

Psychosocial and biological predictors of resident physician burnout.

BACKGROUND: A high proportion of health professionals in training suffer from work-related stress and may develop a burnout syndrome. OBJECTIVES: To study the incidence of burnout after the first year of residency in a teaching hospital and to identify baseline psychological, psychosocial work conditions, and biological risk factors. METHODOLOGY: We assessed the following in a prospective cohort of residents at baseline (first month residence) and after 1 year: background factors (socio-demographics, psychiatric history), perceived stress score (Perceived Stress Scale), Maslach Burnout Inventory score, and psychosocial factors (Job Content Questionnaire). Blood samples were obtained to study serum cortisol, IL-6, and TNF-α concentrations. The cumulative incidence was modelled by multivariate log-binomial regression analysis. RESULTS: We included 71 participants with a female majority (64.8%), age 26.4 (2.65) years, psychiatric history in 20%, and burnout in 13%. Among those without burnout initially (N = 59), it had developed by 1 year in 22% of residents. Increased job demand (RR = 1.259, 95%CI = 1.019-1.556, p = 0.033) and decreased cortisol levels (RR = 0.877, 95%CI = 0.778-0.989, p = 0.032) predicted burnout after 1 year of residency among medical trainees. CONCLUSION: Burnout syndrome develops in 22% of residents by 1 year of training and can be predicted by increased work demands and decreased cortisol levels.

Targeting Microglial Polarization to Improve TBI Outcomes.

Traumatic Brain Injury (TBI) is still the worldwide leading cause of mortality and morbidity in young adults. Improved safety measures and advances in critical care have increased chances of surviving a TBI, however, numerous secondary mechanisms contribute to the injury in the weeks and months that follow TBI. The past 4 decades of research have addressed many of the metabolic impairments sufficient to mitigate mortality, however, an enduring secondary mechanism, i.e. neuroinflammation, has been intractable to current therapy. Neuroinflammation is particularly difficult to target with pharmacological agents due to lack of specificity, the blood brain barrier, and an incomplete understanding of the protective and pathologic influences of inflammation in TBI. Recent insights into TBI pathophysiology have established microglial activation as a hallmark of all types of TBI. The inflammatory response to injury is necessary and beneficial while the death of activated microglial is not. This review presents new insights on the therapeutic and maladaptive features of the immune response after TBI with an emphasis on microglial polarization, followed by a discussion of potential targets for pharmacologic and non-pharmacologic treatments. In aggregate, this review presents a rationale for guiding TBI inflammation towards neural repair and regeneration rather than secondary injury and degeneration, which we posit could improve outcomes and reduce lifelong disease burden in TBI survivors.

Enhanced Nonlinear Optical Coefficients of MAPbI3 Thin Films by Bismuth Doping.

The poor photostability under ambient conditions of hybrid halide perovskites has hindered their recently explored promising nonlinear optical properties. Here, we show how Bi3+ can partially substitute Pb2+ homogeneously in the commonly studied MAPbI3, improving both environmental stability and photostability under high laser irradiation. Bi content around 2 atom % produces thin films where the nonlinear refractive (n2) and absorptive coefficients (ß), which modify the refractive index (Δn) of the material with light fluence (I), increase up to factors of 4 and 3.5, respectively, compared to undoped MAPbI3. Higher doping inhibits the nonlinear parameters; however, the samples show higher fluence damage thresholds. Thus, these results provide a road map on how MAPbI3 can be engineered for practical cost-effective nonlinear applications by means of Bi doping, including optical limiting devices and multiple-harmonic generation into optoelectronics devices.

Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation / Genotoxicidad y citotoxicidad del sevoflurane en dos lineas celulares humanas in vitro con radiacion ionizante

Objective: To determine the in vitro toxicity of different concentrations of sevoflurane in cells exposed to X-ray. Methods: The genotoxic effects of sevofluorane were studied by means of the micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes. Subsequently, its cytotoxic effects on PNT2 (normal prostate) cells was determined using the cell viability test (MTT) and compared with those induced by different doses of X-rays. Results: A dose- and time-dependent cytotoxic effect of sevofluorane on PNT2 cells was determined (p >0.001) and a dose-dependent genotoxic effect of sevofluorane was established (p >0.001). Hovewer, at volumes lower than 30 μL of sevofluorane at 100%, a non-toxic effect on PNT2 cells was shown. Conclusion: sevofluorane demonstrates a genotoxic capacity as determined in vitro by micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes.

Objetivo: Determinar la capacidad genotóxica del anestésico sevofluorano en en células expuestas a radiación ionizante. Métodos: La genotoxicidad del sevofluorane se determinó mediante el test del bloqueo citocinético de linfocitos humanos irradiados bloqueados con citochalasina. La capacidad citotóxica se determinó mediante el test de viabilidad celular e inhibición del crecimiento celular (MTT) en células PNT2 (epiteliales de próstata), comparando sus resultados con los inducidos por diferentes dosis de rayos X. Resultados: Se ha determinado un efecto citotóxico del sevofluorane sobre las células PNT2 que presenta correlación con la dosis administrada y el tiempo de estudio utilizado (p >0.001), así como un efecto genotóxico con características dosis-dependientes (p >0.001). Sin embargo, con volúmenes de sevofluorane puro inferiores a 30 μL no encontramos efecto citotóxico sobre las células PNT2. Conclusión: Sevofluorane muestra una significativa capacidad genotóxica in vitro determinada mediante el test de micronúcleos en linfocitos humanos irradiados con bloqueados citocinético mediante citochalsina.

Dynamics of suspended sediment borne persistent organic pollutants in a large regulated Mediterranean river (Ebro, NE Spain).

Mediterranean rivers are characterized by highly variable hydrological regimes that are strongly dependent on the seasonal rainfall. Sediment transport is closely related to the occurrence of flash-floods capable to deliver enough kinetic energy to mobilize the bed and channel sediments. Contaminants accumulated in the sediments are likely to be mobilized as well during such events. However, whereas there are many studies characterizing contaminants in steady sediments, those devoted to the transport dynamics of suspended-sediment borne pollution are lacking. Here we examined the occurrence and transport of persistent organic microcontaminants present in the circulating suspended sediments during a controlled flushing flow in the low part of the River Ebro (NE Spain) 12 km downstream of a well-known contaminated hot-spot associated to a nearby chloro-alkali industry. Polycyclic aromatic hydrocarbons (PAHs) and semi-volatile organochlorine pollutants (DDT and related compounds, DDX; polychlorinated byphenils, PCBs; and other organochlorine compound, OCs) were measured in the particulate material by GC-MS and GC-MS/MS, using previously developed analytical methods. The concentration levels observed were compared to previously reported values in steady sediments in the same river and discussed on a regulatory perspective. Hydrographs and sedigraphs recorded showed a peak-flow of 1,300 m(3)s(-1) and a corresponding peak of suspended sediments of 315 mg L(-1). Combination of flow discharge, suspended sediments and pollutants' concentrations data allowed for quantifying the mass flows (mass per unit of time) and setting the load budgets (weight amount) of the different pollutants transported by the river during the monitored event. Mean mass-flows and total load values found were 20.2 mg s(-1) (400 g) for PAHs, 38 mg s(-1) (940 g) for DDX, 44 mg s(-1) (1,038 g) for PCBs and 8 mg s(-1) (200 g) for OCs. The dynamic pattern behavior of PAHs differs substantially to that of organochlorine pollutants, thus reflecting different pollution origins.

Depletion study and estimation of the withdrawal period for enrofloxacin in pacu (Piaractus mesopotamicus).

Defining the pharmacokinetic parameters and depletion intervals for antimicrobials used in fish will help in the development of important guidelines for future regulations by Brazilian agencies on the use of these substances in fish farming. This paper presents a depletion study for enrofloxacin (ENR) and its main metabolite, ciprofloxacin (CIP), in pacu (Piaractus mesopotamicus) fillets. The depletion study was carried out under monitored environmental conditions, with the temperature controlled at 27 °C to mimic the fish farming conditions in Brazil. ENR was administered orally via medicated feed for 10 consecutive days at daily dosages of 10 mg/kg body weight (b.w.). The fish were slaughtered at 6, 12, and 24 h and 2, 3, 5, 8, 12, 17, and 24 days after the medication period. Considering a maximum residue limit of 100 µg/kg for the sum of the ENR and CIP residues in the fillet, the results obtained in the depletion study allowed the estimation of a half-life for ENR of 2.75 days and a withdrawal period of 23 days. The results obtained in this study are important for the farming of pacu in tropical regions.

A stable multimodel scheme control for the regulation of the transient behavior of a tunnel-diode trigger circuit.

A multimodel scheme is designed for a triggering tunnel-diode circuit. The scheme improves the transient behavior during the transition time period after switching from a stable system equilibrium point to another one which is known as a triggering process. Each model is obtained by a linearization of the circuit near an equilibrium point. Moreover, each of these models can be described as a combination of two other transfer functions describing the linearized plant behavior near two different equilibrium points. The scheme chooses online the model with the best tracking performance in order to generate the control law. Different reference transfer functions are proposed with the aim of generating the desired transient in the triggering process. Some simulations show the usefulness of this scheme.

Testing abnormality in the spatial arrangement of cells in the corneal endothelium using spatial point processes.

The study of central corneal endothelium morphology is important in Ophthalmology. Some of the pathologies that could compromise endothelial cell morphology are trauma, cataract, surgery, use of contact lenses, corneal dystrophies or degenerations. The quantitative analysis of cell shape and cellular pattern is more sensitive in detecting subtle changes in endothelial morphology than cell density measurement or cell area analysis. In this paper, the morphology of the central cornea, the most important area from the point of view of vision, is studied through an associated bivariate spatial point pattern: the centroids of the cells and the triple points, that is, the points where three different cells converge. Nine different summary descriptors (widely used in the statistical analysis of spatial point patterns) have been used: the empty space distribution function; the nearest neighbour distribution function and Ripley's K-function for each type of point separately (centroids and triple points), plus the corresponding three versions of these functions in the bivariate case. A control sample with similar age and cell density and no known abnormality is associated to each patient. The above descriptors are calculated for the patient and the controls. Each descriptive of the patient is compared with the corresponding descriptors from the controls by means of a graphical analysis and a formal test. Some patients presenting different pathologies are analysed in detail. Endothelia considered morphologically abnormal by visual inspection, which were not detected by hexagonality or density analysis, could be distinguished from control endothelia by these new descriptors.

Functional and biochemical characteristics of a soluble B lymphocyte proliferation-inhibiting activity produced by bone marrow cells from multiple myeloma patients.

Several mechanisms are discussed as inducers for polyclonal hypogammaglobulinemia in multiple myeloma. A soluble noncytotoxic activity which inhibits in vitro the proliferation of normal polyclonal spleen B lymphocytes was measured in the supernatant of cultured bone marrow mononuclear cells from multiple myeloma patients. In addition, human B lymphoblastic cell lines (CESS, Daudi) and human T lymphocytes were sensitive to the antiproliferative effect of the suppressor activity, while other cell lines (RPMI 8226, IM9, CTL6, L1210, HL-60, and K562) were not. The activity was detected in a 5-kDa fraction and was stable to heating (30 min, 56 degrees C) and proteolytic enzymes. Extraction experiments using chloroform:methanol (2:1) suggest a lipid character of the suppressor activity.

[Magnitude of acid gastroesophageal reflux measured by 24-hour esophageal pH monitoring compared to the degree of endoscopic esophagitis]. / Magnitud del reflujo gastroesofágico ácido cuantificado por medición de pH de 24 horas segun el grado de esofagitis endoscópica.

Twenty four hour esophageal pH monitoring was performed in 110 patients, placing a pH electrode 5 cm above the proximal border of the lower esophageal sphincter. This test allows to measure the total lapse in which there is an acid pH in the esophagus, the ability of the esophagus to get rid of the acid reflux and documents the relationship between esophageal pH and symptoms. Upper GI endoscopy showed a normal esophagus in 38 patients, and esophagitis grade I in 25, grade II in 11, grade III in 25 and grade IV in 11. There was a high correlation between the severity of esophagitis and the total time in which the esophagus was exposed to an acid pH. It is concluded that this test can be used as a "gold standard" for gastroesophageal reflux detection.

Enhanced tumor imaging with pokeweed mitogen.

Traditional tumor imaging with biotracer techniques relies solely on the target specificity of the biomolecule. We hypothesize that specific imaging is possible by altering the rate of tissue clearance (both normal and aberrant) of any given radiotracer. Pokeweed mitogen (PWM) as a biomodulator, represents a class of molecules which regulate cellular differentiation and cell-cell interactions and, as part of these mechanisms alter tissue clearance rates (both normal and aberrant). Utilizing the B-16/C57BL/6 model, 7 days post-transplantation (which represents log phase growth of the tumor), 10 animals were imaged following an i.v. injection of 1-2 mCi 99mTc-PWM in order to visualize the tumors and determine the optimal imaging kinetics. A specific tumor image is achieved between 120 and 240 min post-injection. In addition, tumor imaging studies using a non-tumor-specific biomolecule were conducted by injecting 19 animals i.v. with 1-2 mCi of 99mTc-human serum albumin (HSA). Twelve of these animals were given 10 micrograms of PWM i.p. at various intervals prior to the 99mTc-HAS administration. Imaging and biodistribution studies were performed at various intervals up to 2 h post-99mTc-HSA injection. A 32-59% increase in the tumor-to-muscle ratio was observed in the PWM-treated animals relative to the non-treated controls. To further investigate the PWM-induced tissue clearance alteration hypothesis, tissue clearance studies using 99mTc-diethylenetriaminepentaacetic acid (DTPA) were conducted in non-tumor bearing ICR mice and the B-16/C57BL/6 tumor bearing animals. 99mTc-DTPA normal tissue clearance rates were significantly increased in the PWM treated animals relative to the non-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Panorama de la morbilidad infantil en Chile / Overview on childhood morbidity in Chile

Se efectúa una revisión y análisis de la morbilidad en menores de 15 años, con información obtenida de publicaciones biomédicas chilenas de los últimos 7 años y datos del Ministerio de Salud y del Instituto Nacional de Estadística. En general fueron especialmente considerados en ésta revisión aquéllos trabajos de amplia casuística y metodología apropiada. De las fuentes de información se utilizaron esencialmente: a) encuestas poblacionales, b) controles de salud, c) causas de consultas pediátricas y d) egresos hospitalarios. Dentro de los numerosos hechos analizados, merecieron especial atención las enfermedades infecciosas transmisibles, las enteroparasitosis, la sarna, pediculosis, bocio, consumo de sustancias químicas (alcohol, psicotrópicos, tabaco), deficiencias auditivas y visuales. Todos éstos aspectos fueron extensamente discutidos y analizados estableciendo, asimismo, una correlación con medidas preventivas susceptibles de influír en ellos