Effects of artemisinin and cisplatin on the malignant progression of oral leukoplakia. In vitro and in vivo study.

OBJECTIVES: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. METHODS: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. RESULTS: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. CONCLUSION: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.

Individual Patient Data Meta-Analysis of Dynamic Cerebral Autoregulation and Functional Outcome After Ischemic Stroke.

BACKGROUND: The relationship between dynamic cerebral autoregulation (dCA) and functional outcome after acute ischemic stroke (AIS) is unclear. Previous studies are limited by small sample sizes and heterogeneity. METHODS: We performed a 1-stage individual patient data meta-analysis to investigate associations between dCA and functional outcome after AIS. Participating centers were identified through a systematic search of the literature and direct invitation. We included centers with dCA data within 1 year of AIS in adults aged over 18 years, excluding intracerebral or subarachnoid hemorrhage. Data were obtained on phase, gain, coherence, and autoregulation index derived from transfer function analysis at low-frequency and very low-frequency bands. Cerebral blood velocity, arterial pressure, end-tidal carbon dioxide, heart rate, stroke severity and sub-type, and comorbidities were collected where available. Data were grouped into 4 time points after AIS: <24 hours, 24 to 72 hours, 4 to 7 days, and >3 months. The modified Rankin Scale assessed functional outcome at 3 months. Modified Rankin Scale was analyzed as both dichotomized (0 to 2 versus 3 to 6) and ordinal (modified Rankin Scale scores, 0-6) outcomes. Univariable and multivariable analyses were conducted to identify significant relationships between dCA parameters, comorbidities, and outcomes, for each time point using generalized linear (dichotomized outcome), or cumulative link (ordinal outcome) mixed models. The participating center was modeled as a random intercept to generate odds ratios with 95% CIs. RESULTS: The sample included 384 individuals (35% women) from 7 centers, aged 66.3±13.7 years, with predominantly nonlacunar stroke (n=348, 69%). In the affected hemisphere, higher phase at very low-frequency predicted better outcome (dichotomized modified Rankin Scale) at <24 (crude odds ratios, 2.17 [95% CI, 1.47-3.19]; P<0.001) hours, 24-72 (crude odds ratios, 1.95 [95% CI, 1.21-3.13]; P=0.006) hours, and phase at low-frequency predicted outcome at 3 (crude odds ratios, 3.03 [95% CI, 1.10-8.33]; P=0.032) months. These results remained after covariate adjustment. CONCLUSIONS: Greater transfer function analysis-derived phase was associated with improved functional outcome at 3 months after AIS. dCA parameters in the early phase of AIS may help to predict functional outcome.

Exploring Physiological Differences in Brain Areas Using Statistical Complexity Analysis of BOLD Signals.

The brain is a fundamental organ for the human body to function properly, for which it needs to receive a continuous flow of blood, which explains the existence of control mechanisms that act to maintain this flow as constant as possible in a process known as cerebral autoregulation. One way to obtain information on how the levels of oxygen supplied to the brain vary is through of BOLD (Magnetic Resonance) images, which have the advantage of greater spatial resolution than other forms of measurement, such as transcranial Doppler. However, they do not provide good temporal resolution nor allow for continuous prolonged examination. Thus, it is of great importance to find a method to detect regional differences from short BOLD signals. One of the existing alternatives is complexity measures that can detect changes in the variability and temporal organisation of a signal that could reflect different physiological states. The so-called statistical complexity, created to overcome the shortcomings of entropy alone to explain the concept of complexity, has shown potential with haemodynamic signals. The aim of this study is to determine by using statistical complexity whether it is possible to find differences between physiologically distinct brain areas in healthy individuals. The data set includes BOLD images of 10 people obtained at the University Hospital of Leicester NHS Trust with a 1.5 Tesla magnetic resonance imaging scanner. The data were captured for 180 s at a frequency of 1 Hz. Using various combinations of statistical complexities, no differences were found between hemispheres. However, differences were detected between grey matter and white matter, indicating that these measurements are sensitive to differences in brain tissues.

Gallic acid triphenylphosphonium derivatives TPP+-C10 and TPP+-C12 inhibit mitochondrial function in Candida albicans exerting antifungal and antibiofilm effects.

AIMS: To evaluate the antifungal and antibiofilm activity of gallic acid derivatives TPP+-C10 and TPP+-C12 and their effects on mitochondrial function on two Candida albicans reference strains (ATCC 90029 and ATCC 10231). METHODS AND RESULTS: First, we determined minimal inhibitory concentration (MIC) using a microdilution assay. Both compounds exerted antifungal effects, and their MICs ranged from 3.9 to 13 µM, with no statistically significant differences between them (P > 0.05, t-test). These concentrations served as references for following assays. Subsequently, we measured oxygen consumption with a Clark electrode. Our observations revealed that both drugs inhibited oxygen consumption in both strains with TPP+-C12 exerting a more pronounced inhibitory effect. We then employed flow cytometry with TMRE as a probe to assess mitochondrial membrane potential. For each strain assayed, the compounds induced a decay in transmembrane potential by 75%-90% compared to the control condition (P < 0.05, ANOVA). Then, we measured ATP levels using a commercial kit. TPP+-C12 showed a 50% decrease of ATP content (P < 0.05 ANOVA), while TPP+-C10 exhibited a less pronounced effect. Finally, we assessed the antibiofilm effect using the MTT reduction assay. Both compounds were effective, but TPP+-C12 displayed a greater potency, requiring a lower concentration to inhibit 50% of biofilms viability (P < 0.05, t-test). CONCLUSIONS: Derivatives of gallic acid linked to a TPP+ group exert antifungal and antibiofilm activity through impairment of mitochondrial function in C. albicans.

Detection of Blood CO2 Influences on Cerebral Hemodynamics Using Transfer Entropy.

Cerebral hemodynamics describes an important physiological system affected by components such as blood pressure, CO2 levels, and endothelial factors. Recently, novel techniques have emerged to analyse cerebral hemodynamics based on the calculation of entropies, which quantifies or describes changes in the complexity of this system when it is affected by a pathological or physiological influence. One recently described measure is transfer entropy, which allows for the determination of causality between the various components of a system in terms of their flow of information, and has shown positive results in the multivariate analysis of physiological signals. This study aims to determine whether conditional transfer entropy reflects the causality in terms of entropy generated by hypocapnia on cerebral hemodynamics. To achieve this, non-invasive signals from 28 healthy individuals who undertook a hyperventilation maneuver were analyzed using conditional transfer entropy to assess the variation in the relevance of CO2 levels on cerebral blood velocity. By employing a specific method to discretize the signals, it was possible to differentiate the influence of CO2 levels during the hyperventilation phase (22.0% and 20.3% increase for the left and right hemispheres, respectively) compared to normal breathing, which remained higher during the recovery phase (15.3% and 15.2% increase, respectively).

Traumatismo cervical por arma de fuego en pediatría: apropósito de un caso

RESUMEN Introducción: Las lesiones cervicales por arma de fuego en pediatría tienen baja incidencia, aproximadamente a 5 a 10%, con una mortalidad de 0 a 11%. Objetivo: Describir un caso de politraumatismo por arma de fuego, su manejo multidisciplinario y las consecuencias de la imprudencia a la exposición de niños a las mismas. Caso Clínico: Paciente de sexo masculino, de 13 años de edad, con traumatismo de cara, cuello y tórax por herida accidental por arma de fuego (escopeta) con diagnósticos: Trauma Facial: fractura de maxilar superior e inferior; Trauma de cuello: lesión en cuerpo vertebral C4/C7 con perdigones incrustados; Trauma de tórax: contusión pulmonar derecha; Trauma de partes Blandas: con perdigones incrustados en celular subcutáneo. Ingresa al hospital de Trauma en choque hipovolémico presentando casi inmediatamente paro cardiorespiratorio, respondiendo a reanimación cardiopulmonar avanzada. TAC de cráneo al ingreso normal; al 8vo día se evidencia esquirla en sistema venoso de la base; TAC de cuello: se evidencia desplazamiento de tráquea y aire peri tráquea; AgioTAC: pseudoaneurisma en carótida interna izquierda. Fibrobroncospcopía: contusiones a nivel de tráquea; EDA: esófago y estómago con erosiones cubiertas por fibrina sin evidencia de fístula o perforación de víscera hueca. Tratamiento: en Asistencia Mecánica Respiratoria (ARM) por 10 días; inotrópicos por 72 hs, se realiza reparación de arteria carótida interna; colocación de arco de Erich por cirujanos maxilofaciales. Alta a sala de pediatría con buena evolución.

ABSTRACT Introduction: Pediatric cervical gun injuries have a low incidence, approximately 5 to 10%, with a mortality of 0 to 11%. Clinical Case: a 13-year-old male patient who presented with trauma to the face, neck and thorax due to accidental firearm injury (shotgun) with the following diagnoses: Facial trauma: fracture of the upper and lower jaw; Neck trauma: C4 / C7 vertebral body injury with embedded pellets; Chest trauma: right pulmonary contusion; Soft tissue trauma: embedded pellets in subcutaneous soft tissue. He was admitted to the Trauma hospital in hypovolemic shock, presenting almost immediate cardiorespiratory arrest, which responded to advanced cardiopulmonary resuscitation. CT scan of the skull was normal at admission; on the 8th day it showed evident splintering in the basal venous system; CT of the neck: tracheal displacement and evident peri-tracheal air; Angio CT: pseudoaneurysm in left internal carotid artery. Fibrobronchoscopy: bruises at the tracheal level; EDA: esophagus and stomach with fibrin-covered erosions without evidence of fistula or hollow viscera perforation. Treatment: on Mechanical Respiratory Assistance (MRA) for 10 days; inotropes for 72 hours, internal carotid artery repair was performed, Erich arch placement by maxillofacial surgeons. He was discharged to the pediatric ward with favorable evolution.

Activación de la célula T, alteraciones en el lupus eritematoso sistémico, una revisión narrativa / T-cell activation, alterations in systemic lupus erythematosus: A narrative review

Resumen La activación de los linfocitos T se inicia a través de la presentación de antígenos endógenos o exógenos por células presentadoras de antígenos a través del complejo mayor de histocompatibilidad, el cual se une a un receptor especializado presente en los linfocitos T. Este reconocimiento desencadena una cascada de señalización intracelular que conlleva a un aumento en la expresión de integrinas, modificaciones del citoesqueleto y producción de factores de transcripción involucrados en la liberación de citocinas y mediadores inflamatorios. Uno de los inductores más importantes en la activación celular es el complejo enzimático con acción tirosina cinasa. Las cinasas que pertenecen a la familia SRC (SFK), FYN y LCK están involucradas en un gran número de procesos importantes en la activación, modulación de la respuesta linfocitaria y el desarrollo de enfermedades autoinmunes. La regulación de la señalización de las cinasas, así como de proteínas adaptadoras involucradas en la activación del linfocito T, son fundamentales para mantener el umbral de activación y modulación de la respuesta del linfocito. La fosforilación de sitios de regulación positiva de estas proteínas es importante para permitir una configuración activa de la proteína y de esta forma su máxima capacidad como cinasa. La fosforilación de los sitios de regulación negativa conlleva a una configuración cerrada de la proteína de tal forma que reduce su función de cinasa e inhibe su función. Las alteraciones en la señalización por modificación de algunas proteínas citoplasmáticas se asocian en algunos casos al desarrollo de enfermedades autoinmunes, como el lupus eritematoso sistémico. En condiciones fisiológicas, el complejo receptor de linfocitos T se reagrupa con complejos proteicos que interactúan armónicamente para generar una sen al interna. Los eventos de señalización alterados son en parte los responsables de una expresión anómala de citocinas, entre ellas la interleucina-6 (IL-6), IL-10, IL-2, IFN y CD40 ligando; estas modificaciones alteran la capacidad de los linfocitos T para sobre estimular a los linfocitos B, traduciéndose en un aumento en la producción de autoanticuerpos y en el desencadenamiento de la enfermedad autoinmune.

Abstract The activation of T cells is initiated by the presentation of exogenous or endogenous antigens, by antigen presenting cells through the major histocompatibility complex, which binds to a special receptor on T cells. This acknowledgement triggers a cascade of intracellular signalling that leads to an increase in integrin expression, cytoskeletal modifications, and transcription factors production involved in the liberation of cytokines and inflammatory mediators. One of the most important inducers in cell activation is the enzymatic complex with tyrosine kinase action. The kinases which belong to the SRC (SFK) LCK and FYN family have been involved in a large number of important processes in the activation and modulation of the T cells response, as well as in the development of autoimmune diseases. Regulating the kinases signalling, as well as the adapter proteins involved in T cell activation, is essential for maintaining an activation threshold, as well as the modulation of cell response. The phosphorylation of the positive regulation sites of these proteins is important to allow an active configuration of the protein and thereby its maximum capacity as kinase. The phosphorylation of negative regulation sites leads to a closed configuration of the protein that reduces its kinase function, and thereby inhibits its own function. The alteration in signalling by the modification of certain cytoplasmic proteins in some cases is associated with the development of autoimmune diseases, such as systemic lupus erythematosus. Under physiological conditions the T cell receptor complex regroups with protein complexes that interact harmonically to generate an internal signal. The altered signalling events are partly responsible for an anomalous expression of cytokines, including the interleukin-6 (IL-6), IL-10, IL-2, IFN, and CD40 linking, these modifications affects the cells ability to over-stimulate T and B cells, resulting in an increased production of autoantibodies and the triggering of the autoimmune disease.

Guía de práctica clínica para el tratamiento de la agitación psicomotora y la conducta agresiva / Clinical practice guidelines for the treatment of psychomotor agitation and aggressive behavior

Se presenta la Guía de práctica clínica para el tratamiento de la agitación psicomotora y la conducta agresiva del Departamento de Emergencia del Instituto Nacional de Salud Mental ôHonorio Delgado û Hideyo Noguchiõ Lima, Perú, aprobada mediante la Resolución Directoral Nº 071-2013-DG/INSMõHD-HNõ.

We present the Clinical practice guidelines for the treatment of psychomotor agitation and aggressive behavior from the Emergency Department, Instituto Nacional de Salud Mental ôHonorio Delgado û Hideyo Noguchiõ Lima, Peru, approved by Resolución Directoral Nº 071-2013-DG/INSMõHD-HNõ.

Endocarditis infecciosa: características clínicas, complicaciones y mortalidad en 506 pacientes y factores pronósticos de sobrevida a 10 años (1998-2008). Estudio cooperativo nacional en endocarditis infecciosa en Chile (ECNEI-2) / Clinical characteristics, complications and mortality in 506 patients with infective endocarditis and determinants of survival rate at 10 years

Background: Rates ofmorbidity and mortality in Infective Endocarditis (IE) remain high and prognosis in this disease is still difficult and uncertain. Aim: To study IE in Chile in its active phase during inpatient hospital stay and long term survival rates. Material and Methods: Observational prospective national cohort study of 506 consecutive patients included between June 1,1998 and July 31, 2008, from 37 Chilean hospitals (secondary and tertiary centers) nationwide. Results: The main findings were the presence of Rheumatic valve disease in 22.1 % of patients, a history of intravenous drug abuse (IVDA) only in 0.7%, the presence of Staphylo-coccus aureus in 29.2% of blood cultures, negative blood cultures in 33.2%, heart failure in 51.7% and native valve involvement in 86% ofpatients. Echocardiographic diagnosis was achieved in 94% of patients. Hospital mortality was 26.1% and its prognostics factors were persisting infection (Odds ratio (OR) 6.43, Confidence Interval (CI) 1.45-28.33%), failure of medical treatment and no surgical intervention (OR 48.8; CI 6.67-349.9). Five and 10 years survival rates were 75.6 and 48.6%, respectively. The significant prognostic factors for long term mortality, determined by multivariate analysis were the presence of diabetes, Staphylococcus aureus infection, sepsis, heart failure, renal failure and lack of surgical treatment during the IE episode. Conclusions: The microbiologic diagnosis of IE must be urgently improved in Chile. Mortality rates are still high (26.1%) partly because of a high incidence of negative blood cultures and the need for more surgical valve interventions during in-hospital period. Long term prognostic factors for mortality should be identified early to improve outcome.

Psicosis cicloides: a propósito de dos probables casos / Cycloid psychosis: regarding two probable cases

Cases of acute psychosis which during longitudinal follow-up did not meet criteria for schizophrenic psychosis or affective psychosis are common in clinical practice; however, those cases can be classified into diagnostic categories that are not sufficiently representative of their nosological individuality. This intermediate group of psychosis: characterized by acute onset, usually brief course, polymorphic symptomatology and recovery without defect, has been conceived in different psychiatric schools through different concepts: in this sense, the construct of Cycloid Psychoses, original from German psychiatry, has demonstrated validity and is embedded in a heuristically profitable diagnostic system (the Wernicke-Kleist-Leonhard classification). Apropos of two representative cases, we review here the relevant literature and highlight the need to consider this diagnostic possibility - not fully considered in the present diagnostic systems yet- in order to avoid prolonged antipsychotic treatments based on unnecessarily ominous nosological hypothesis.

Los casos de psicosis aguda que durante el seguimiento longitudinal no reúnen criterios de esquizofrenia ni de psicosis afectivas son frecuentes en la práctica clínica habitual; sin embargo, pueden ser catalogados dentro de categorías diagnósticas que no representan de modo suficiente su individualidad nosológica. Este grupo intermedio de psicosis: caracterizado por su inicio agudo, curso usualmente breve, sintomatología polimórfica y recuperación sin defecto, ha sido concebido en diferentes escuelas psiquiátricas mediante diferentes conceptos: en tal sentido, el constructo de Psicosis Cicloides, proveniente de la psiquiatría alemana, ha demostrado validez y se halla engarzado en un sistema diagnóstico heurísticamente valioso (el de Wernicke-Kleist-Leonhard). A propósito de dos casos representativos, revisamos la literatura pertinente y resaltamos la necesidad de considerar esta posibilidad diagnóstica, a fin de evitar prolongados y potencialmente perjudiciales tratamientos antipsicóticos, prescritos bajo hipótesis incorrectas y gravosas.

Seguridad de la angioplastía coronaria ambulatoria por vía transradial: experiencia de un centro / Safety of trans-radial ambulatory coronary angioplasty: a single center experience

Introducción: El número creciente de intervenciones coronarias ha generado una demanda mayor de camas hospitalarias. Se ha reportado que luego de un periodo postintervención de 4 a 6 horas no se observan complicaciones asociadas a la angioplastía coronaria (AC). Objetivo: Evaluar la seguridad del alta precoz luego de la angioplastía coronaria. Material y métodos: Se analizaron los pacientes (pts) sometidos a AC y dados de alta luego de una observación de 4 horas, en el período comprendido entre Enero 2004 y Agosto 2010. Se analizaron las variables clínicas y angiografías. Se consideraron criterios de seguridad: infarto y/o trombosis del stent, complicaciones hemorrágicas y mortalidad hasta los 30 días. Resultados: Se realizó AC ambulatoria a 414 pacientes con una edad de 63.17 +/- 10.4 años. 80 por ciento fueron hombres. El 53 por ciento fueron portadores de enfermedad de 2 y 3 vasos. La AC fue exitosa en el 95.9 por ciento de casos. El 49 por ciento de las lesiones tratadas fueron de complejidad mayor (tipo B2 y C). Se analizaron los índices de seguridad en tres periodos: 4 a 24 horas, 24 horas a 7 dias y de 7 días a 30 días, observándose solo 3 hemorragias menores en el período más precoz y ningún sangramiento mayor, nueva revascularización, infarto agudo del miocardio, accidente cerebrovascular, ni mortalidad en ninguno de los tiempos analizados. Conclusión: El alta precoz luego de la AC por vía radial es un procedimiento seguro independiente de la complejidad de la anatomía coronaria.

The increasing number of percutaneous coronary angioplasty (PTCA) procedures poses a strain on the availability of hospital. There is evidence that no complications of PTCA are observed 4 o 6 hr after the procedure. Aim: To evaluate the safety of early discharge after PTCA Methods: Patients submitted to PTCA from January to August 2010 who were discharged after a 4 hr observation period had their clinical and angiographic characteristics assessed. Infarction, stent thrombosis and 30 day mortality were determined. Results: 414 patients were included. Mean age was 63.2 years (SD 10.4), 80 percent of them males. 53 per cent had 2 or 3 vessel disease. PTCA was successful in 95.9 percent of cases. 49 per cent of coronary artery lesions were type B2 or C. 3 minor bleeding episodes occurred before 24 hr after the procedure. No major bleedings, new revascularization, acute myocardial infarction, stroke were seen up to 30 days post procedure. There was no mortality. Conclusion: Early discharge after trans-radial artery PTCA is safe even for treatment of complex coronary artery lesions.

Comparación del estadío clínico de presentación del adenocarcinoma gástrico en Arequipa entre los periodos 1991-1992 y 2001-2002 / Comparison of the clinical stage of presentation of gastric adenocarcinoma in Arequipa between the periods 1991-1992 and 2001-2002

Objetivos: Comparar los estadíos de presentación del adenocarcinoma gástrico en Arequipa entre los periodos 1991-1992 y 2001-2002 e identificar posibles características epidemiológicas que estuvieran influyendo en el momento del diagnóstico. Material y métodos: El estudio fue transversal, retrospectivo, descriptivo y analítico. Se estudiaron 47 casos del primer periodo y 65 del segundo. Ambos periodos fueron comparados en cuanto a estadío de presentación y otras variables epidemiológicas. Resultados: Aunque en ambos periodos la gran mayoría de casos debutaron en estadío IV (87 por ciento y 72 por ciento, respectivamente), se observó, en el segundo periodo, una reducción considerable de casos diagnosticados en estadíos avanzados (IIIB y IV), en comparación al primero; además hubo un aumento de casos diagnosticados en estadíos tempranos (IA, IB, II y IIIA). Los casos de early cáncer ascendieron de 2 por ciento a 9 por ciento. La única variable que presentó diferencia significativa entre periodos fue el porcentaje de pacientes sometidos a endoscopía, siendo mayor en el segundo. Conclusiones: Las cifras encontradas muestran que, a pesar de la variación positiva, aún se detecta en Arequipa el adenocarcinoma gástrico en estadíos muy avanzados, probablemente por falta de equipos e infraestructura moderna.

Estudio de hipertensión arterial en un servicio de urgencia / Study in arteria hypertension in an emergency service

La hipertensión arterial (HTA) es una patología de alta prevalencia en la población general y está relacionada directamente con múltiples afecciones que son frecuentemente atendidas en servicios de urgencia. Su manejo agudo si bien ha sido normado, no siempre es llevado a cabo en forma adecuada. Se estudió en forma retrospectiva la incidencia de HTA (definida como PAS>160 y/o PAD>100 mm Hg) en el Servicio de Urgencia del Hospital Clínico Universidad de Chile, entre el 1 de enero y el 30 de junio del año 2000. Se evaluó para cada paciente el peso, la edad, la presión arterial (agrupando hallazgos, urgencias y emergencias hipertensivas) y frecuencia cardíaca al ingreso, diagnóstico, forma de presentación y tratamiento. A partir de los resultados concluimos que la HTA es una patología de presentación frecuente en nuestro Servicio de Urgencia. Un gran porcentaje corresponde a hallazgos hipertensivos que no requieren tratamiento específico. Existe aún un significativo uso de Nifedipino de acción corta, pese a que no es recomendado