Enolase from Trypanosoma cruzi is inhibited by its interaction with metallocarboxypeptidase-1 and a putative acireductone dioxygenase.

Purification of enolase (ENO) from the cytosol of Trypanosoma cruzi indicated that it may interact with at least five other proteins. Two of them were identified as metallocarboxypeptidase-1 (TcMCP-1) and a putative acireductone dioxygenase (ARDp). Subcellular localization studies confirmed the presence of ARDp in the cytosol, as is the case for ENO and TcMCP-1. Analysis of the ARDp sequence showed that this protein has two domains, an N-terminal ARD and a C-terminal TRP14 (thioredoxin-related protein) domain. The interactions between ENO, TcMCP-1 and ARDp were confirmed for the natural proteins from the trypanosome (using size-exclusion chromatography and co-immunoprecipitation from a cytosolic fraction) and recombinant forms (using ELISA ligand-binding assay and ENO activity assays). The ELISA ligand-binding assays permitted to verify the optimal physicochemical conditions for the interactions (representative for the physiological conditions) and to determine the affinity constants (Kd): ENO/ARDp: 9.54 ±â€¯0.82 nM, ARDp/ENO 10.05 ±â€¯1.11 nM, and ENO/TcMCP-1: 5.66 ±â€¯0.61 nM. The data also show that the interaction between TcMCP-1 and ARDp is mediated by ENO acting as a "bridge". Furthermore, considerable inhibition of the ENO activity, up to 85%, is observed when the enzyme interacts with TcMCP-1 and ARDp simultaneously. All these data confirm that the interaction between ENO, TcMCP-1 and ARDp, occurring in T. cruzi's cytosol, modulates the ENO activity and suggest a possible physiological mechanism for regulation of the ENO activity by the protein-protein interaction.

[Pediatric traumatic brain injury due to civil gunshot wounds at a General Hospital in Cali, Colombia]. / Traumatismo craneoencefálico pediátrico secundario a heridas por arma de fuego en un Hospital General en Cali, Colombia.

OBJECTIVES: Traumatic brain injury (TBI) due to gunshot-wounds (GSW) is a critical situation in the pediatric population. The aim of this study is to characterize TBI in this population since there are few reports that describe it especially in Colombia where its incidence is high, also to determine which were the main mortality predictor within our population. MATERIAL AND METHODS: We conducted a retrospective cross-sectional study in which we reviewed pediatric medical records of patients that had consulted at the Fundacion Valle del Lili pediatric Emergency Room between January of 2011 and December of 2015 because of TBI due to GSW. A descriptive statistical analysis was performed. RESULTS: In our sample of 32 patients the average age was of 13.3 (SD ± 5.4) and with 75% male patients. In our sample the Glasgow Coma Scale (GCS) at entry was less than 8 in 59.38%, a 15.6% needed craniotomy and 81.2% were admitted to the Intensive Care Unit (ICU). Death occurred in 43.75% of cases. The following mortality predictors were obtained: GCS at entry, pupillary exam and light reflexes, ISS, Marshal Score, absence of basal cisterns and presence of subarachnoid hemorrhage in CT scan, and APACHE II. CONCLUSIONS: TBI due to GSW is a devastating entity, especially in the pediatric population, they are responsible of high mortality and disability rates. There were no significant findings regarding infection rates and the use of surgery as a preventive method, therefore there's a chance it might not be indicated.

OBJETIVO: El traumatismo craneoencefálico (TCE) secundario a heridas por arma de fuego (HPAF) es una situación crítica, especialmente en la población pediátrica. El objetivo de este estudio es caracterizar el TCE en esta población dado que existen pocos reportes al respecto, especialmente en Colombia, y determinar cuáles fueron los principales predictores de mortalidad en nuestra población. MATERIALES Y METODOS: Se realizó un estudio descriptivo retrospectivo en el cual se revisaron historias clínicas pediátricas de aquellos pacientes que consultaron al servicio de urgencias de la Fundación Valle del Lili entre enero de 2011 y diciembre de 2015 por TCE debido a HPAF. Se ejecutó un análisis estadístico descriptivo con las variables a considerar. RESULTADOS: Se obtuvo una muestra de 32 pacientes con una edad promedio de 13,3 (SD ± 5,4) y de predominio masculino (75%). Se encontró que el Glasgow Coma Scale (GCS) de ingreso < 8 se presentó en el 59,38% de los casos con un 15,6% que requirieron craniectomía y un 81,2% fue hospitalizado en Unidad de Cuidado Intensivo (UCI). El 43,75% fallecieron. Se obtuvieron los siguientes predictores de mortalidad: GCS de ingreso, examen y reflejos pupilares, ISS, Marshall Score, cisternas basales cerradas y presencia de hemorragia subaracnoidea en la tomografía axial computarizada y APACHE II. CONCLUSIONES: En la presente serie, no se encontró evidencia significativa entre los pacientes tratados quirúrgicamente o no, lo cual podría sugerir que un manejo conservador, individualizando cada caso, es una conducta aceptable y segura.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Qualitative evaluation of Pb and Cu in fish using laser-induced breakdown spectroscopy with multipulse excitation by ultracompact laser source.

We show a new laser-induced breakdown spectroscopy (LIBS) setup based on a small, ultracompact, and low-cost excitation source developed by the authors. The laser is a compact Nd:YAG laser emitting in the multipulse Q-switch regime and is capable of delivering a bunch of pulses with a total energy up to 300 mJ. The developed system is applied to the analysis of Pb and Cu contaminants on fish. LIBS spectra were obtained from scales, muscle, and skin of fresh and frozen samples. The developed excitation source is able to detect 0.25 mg/Kg and 0.20 mg/Kg of Pb and Cu, respectively. In this way, the equipment seems to be adequate to achieve a screening analysis of those contaminants.

In vitro susceptibility of Brazilian Pythium insidiosum isolates to essential oils of some Lamiaceae family species.

The present study aimed to evaluate the in vitro antimicrobial action of Origanum vulgare, Origanum majorana, Mentha piperita and Rosmarinus officinalis on Pythium insidiosum oomycete zoospores. The antimicrobial activity evaluation was performed by the broth microdilution method according to CSLI M38-A2 documentation adapted to phytopharmaceuticals. Twenty-two P. insidiosum isolates were evaluated, and the minimum inhibitory concentration was determined at 100% growth inhibition. All P. insidiosum isolates evaluated showed a minimum inhibitory concentration ranging from 0.05 to 1.75 mg/mL when O. vulgare oil was used and from 0.11 to 3.5 mg/mL for O. majorana, M. piperita and R. officinalis oils. The results obtained indicate that the essential oils tested showed antimicrobial activity on P. insidiosum, with O. vulgare essential oil showing the best performance. These findings emphasize the potential use of plant essential oils as control agents in P. insidiosum infections; further research, however, is needed so as the in vivo activity of these oils can also be evaluated.

Validation of surrogate indexes of insulin sensitivity in acute phase of myocardial infarction based on euglycemic-hyperinsulinemic clamp.

The decrease in insulin sensitivity (IS) during myocardial infarction (MI) is recognized as a possible contributor to poor patient outcomes. Despite its potential relevance, a standardized and convenient IS assessment tool has yet to be established for said clinical scenarios. This study aimed to validate the accuracy of surrogate indexes in determining IS in acute MI patients by comparison with the gold standard reference method for measuring IS, the euglycemic-hyperinsulinemic clamp (EHC). We performed EHCs in 31 consecutive nondiabetic patients who were admitted within the first 24 h of symptoms of ST-segment elevation MI. Patients with prior diagnosis of diabetes, use of hypoglycemic agents, or a glycosylated hemoglobin ≥6.5% were excluded. EHCs were performed at the second day (D2) and sixth day (D6) post-MI. Basal (12-h fasting) blood samples from D2 and D6 were used to evaluate patient blood glucose and insulin levels. We then calculated the following surrogate indexes: homeostatic model assessment of insulin sensitivity (HOMA2S), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). The IS index measured by EHC (ISiclamp) was correlated to HOMA2S, HOMA-IR, and QUICKI at D2 (r = 0.485, P = 0.009; r = -0.384, P = 0.048; r = 0.479, P = 0.01, respectively) and D6 (r = 0.621, P = 0.002; r = -0.576, P = 0.006; r = 0.626, P = 0.002, respectively). Receiver operator characteristic curves made for discrimination of ISiclamp above the median in D2 and D6 depicted areas under the curve of 0.740, 0.734, and 0.760 for HOMA2S, HOMA-IR, and QUICKI, respectively. Bland-Altman plots displayed no apparent systematic error for indexes, but a propensity for proportional error, particularly with HOMA-IR. Thus, based on EHC, these simple surrogate indexes are feasible for assessing IS during MI.

In vitro susceptibility of zoospores and hyphae of Pythium insidiosum to antifungals.

OBJECTIVES: The purpose of this study was to compare the in vitro susceptibilities of 22 Brazilian isolates of Pythium insidiosum to antifungals using a standardized inoculum of zoospores and a proposed novel inoculum prepared from cultured mycelia (hyphae) of P. insidiosum. METHODS: A zoospore suspension of P. insidiosum was obtained by the zoosporogenesis technique. The hyphal inoculum was prepared from a suspension of P. insidiosum mycelium. Susceptibility to each drug was evaluated using the CLSI M38-A2 method. RESULTS: Of the 88 MIC comparisons performed, 36 (41%) showed the same MIC value for the two inocula. The agreement (differences not greater than one dilution) between MICs obtained with both types of inocula was 39.8% (35/88). In other MIC comparisons analysed, 17 (19.3%) showed differences of two or three dilutions. CONCLUSIONS: We conclude that the use of hyphal inocula of P. insidiosum for in vitro susceptibility tests could be a suitable method for evaluating antimicrobial susceptibility, particularly when it is not possible to obtain a standardized zoospore inoculum.

Genetic variation and gains in resistance of strawberry to Colletotrichum gloeosporioides.

Anthracnose crown rot is an important disease of strawberry primarily caused by Colletotrichum gloeosporioides in Florida and North Carolina. Information on the magnitude of additive and nonadditive genetic variation is required to define breeding strategies and to estimate potential genetic gains. However, little is known about the genetic control of resistance and its utility in breeding. Our objectives were to obtain estimates of heritabilities and of components of genetic variances, genotype-environment interactions, and gains for resistance, and to examine the effects of locations and transplant types on the estimates. An incomplete diallel mating design generated 42 full-sib families, which were propagated in plugs from seed (seedling tests) and as bare-root runner plants (clonal tests) of different genotypes of the same families. Both seedlings and clones were inoculated with C. gloeosporioides under field conditions in North Carolina and Florida during the 2010-11 season. Narrow-sense heritability (h(2)) and broad-sense heritability (H(2)) for both clones and seedlings were higher at the North Carolina location (h(2) = 0.34 to 0.62 and H(2) = 0.46 to 0.85) than at the Florida location (h(2) = 0.16 to 0.22 and H(2) = 0.37 to 0.46). Likewise, the seedling tests showed higher genetic control than the clonal tests at both locations. Estimates of dominance variance were approximately one-third of the additive variance at North Carolina and were even larger at Florida. Epistasis was negative at both locations and assumed zero for heritability (H(2)) calculations. Genotype-environment interactions were different by transplant type, suggesting rank changes across locations. 'Pelican' was the most resistant parent at both locations, followed by 'NCH09-68' at the NC location and 'Winter Dawn' at the Florida location. Selection and deployment of the most resistant clone within each of the five best families is estimated to produce average genetic gains of 53.0 and 73.7% at the North Carolina and Florida locations, respectively.

Increasing serum calcium levels and recent return from transplantation as clues to the tuberculous nature of refractory peritoneal dialysis peritonitis.

Peritoneal tuberculosis is an uncommon complication of peritoneal dialysis in Europe. It is more common in Asian immigrants. A delayed diagnosis is frequent and impairs patient outcomes. We present two cases of peritoneal tuberculosis with common features that may help suspect the disease early countries with a low incidence. Both patients were females (of Spanish origin) who had recently restarted peritoneal dialysis following kidney transplantation. Both developed bacterial peritonitis clinically that was refractory to conventional antibiotics, despite clearance of bacteria. Both stopped calcium-containing phosphate binders because of increasing serum calcium that in one case led to frank hypercalcemia that persisted despite low calcium dialysate. Peritoneal biopsy was the first positive test in both cases. This report emphasizes the recent return from transplantation and rising serum calcium levels as features that should alert the physician of a potential underlying tuberculous peritonitis.

First record of a bicephalic embryo of smalltail shark Carcharhinus porosus.

This study reports the first bicephalic embryo of smalltail shark Carcharhinus porosus, which was removed from a pregnant female in coastal waters of the tropical eastern Pacific Ocean. The observation suggested that although the individual's body was well formed, the malformation of the head would have affected it survival.

Prognostic value of the biomarkers procalcitonin, interleukin-6 and C-reactive protein in severe sepsis.

AIM: To determine the prognostic value of the biomarkers procalcitonin, interlukin-6 and C-reactive protein in septic patients. DESIGN: A cohort of 81 septic patients. SETTING: Critical Care Unit. Dr. Peset Hospital. Valencia (Spain). PATIENTS: Divided according to sepsis classification (sepsis, severe sepsis and septic shock), source and two different groups (medical and postsurgical). VARIABLES ANALYZED: Quantitative (procalcitonin, interleukin-6, C-reactive protein, lactate, age, Apache II and SOFA scores upon admission and after 3 and 7 days). Qualitative (ICU mortality, multiorgan failure development and sex). STATISTICAL ANALYSIS: Mann-Whitney U-test for the comparison of quantitative variables, χ² test for qualitative variables. Multivariate analysis with mortality and multiorgan failure as dependent variables and the described quantitative parameters as independent variables. ROC curves of the variables found to be significant in the multivariate analysis. RESULTS: Septic shock patients showed greater mortality and more frequent multiorgan failure. Comparison of survivors versus deceased patients showed significant differences in Apache II score, interleukin-6 and lactate (p<0.001) upon admission and after 3 and 7 days. Similar findings applied to the comparison of patients with and without multiorgan failure, and on the same days. Procalcitonin only showed differences on days 3 and 7 (p=0.001). In the multivariate analysis with mortality as dependent variable, interleukin-6 proved significant on day 3 (OR 2.6). With multiorgan failure as dependent variable, only the SOFA score showed significance (OR 2.3). The Apache II and interleukin-6 ROC curves corresponding to day 3 showed areas of 0.80 and 0.86, respectively. CONCLUSIONS: 1) Interleukin-6 is an inflammatory biomarker with mortality prognostic value. 2) None of the biomarkers proved predictive of multiorgan failure.

Short-term outcomes of patients with a long stay in an internal medicine service.

OBJECTIVE: To describe the characteristics and short-term prognostic factors of patients with prolonged stay in internal medicine. MATERIAL AND METHODS: Retrospective case series study including patients admitted to an Internal Medicine service of a university hospital with lengths of stay greater than 30 days during 5 years. Information was obtained from the Minimum Basic Data Set. Outcome variables were a very long length of stay, in-hospital mortality, and adverse outcomes in the first 30 days after discharge. RESULTS: Out of 11,948 patients, 335 (2.8%) cases had a prolonged stay. The total length of stay was 15,271 days (15% of the total length of stay of the service). The mean age was 74.5 (±13.9) years, 180 (53.7%) were male. The median length of stay was 39 (RIC 34-49) days. Intensive Care Unit admission (OR = 2.5; 95%CI 1.4-4.7; p = 0.003) and receiving a geriatric assessment (OR = 0.3; 95%CI 0.8-0.9; p = 0.042) were independent factors with an effect on very long length of stay. Having an admission in the previous year was an independent factor for an adverse outcome 30 days after discharge (OR = 2.2; 95%CI 1.0-4.8). CONCLUSIONS: The percentage of patients with prolonged length of stay is less than 3%, but they have a high impact on the activity of an internal medicine service. There are factors associated with a very long length of stay and with the presence of an early adverse outcome after discharge.

Survey of coccidia on commercial broiler farms in Colombia: frequency of Eimeria species, anticoccidial sensitivity, and histopathology.

Avian coccidiosis continues to be one of the costliest diseases of commercial poultry. Understanding the epidemiology of Eimeria species in poultry flocks and the resistance profile to common anticoccidials is important to design effective disease prevention and control strategies. This study examined litter samples to estimate the prevalence and distribution of Eimeria species among broiler farms in 4 geographic regions of Colombia. A total of 245 litter samples were collected from 194 broiler farms across representative regions of poultry production between March and August 2019. The litter samples were processed for oocysts enumeration and speciation after sporulation. End-point polymerase chain reaction (PCR) analysis was conducted to confirm the presence of Eimeria species. Anticoccidial sensitivity was determined with 160 Ross AP males in 5 treatment groups: noninfected, nonmedicated control (NNC), infected, nonmedicated control (INC), infected salinomycin treated (SAL, dose: 66 ppm), infected diclazuril treated (DIC, dose: 1 ppm), and infected methylbenzocuate-Clopidol treated (MET.CLO, dose: 100 ppm), All birds were orally inoculated with 1 × 106 sporulated oocysts using a 1 mL syringe, except for the NNC- group who received 1ml of water.Eimeria spp. were found in 236 (96.3%) out of 245 individual houses, representing 180 (92.8%) out of 194 farms. Eimeria acervulina was the most prevalent species (35.0%) followed by Eimeria tenella (30.9%), Eimeria maxima (20.4%), and other Eimeria spp. (13.6%). However, mixed species infections were common, with the most prevalent combination being mixtures of E. acervulina, E. maxima, E. tenella, and other species in 31.4% of the Eimeria-positive samples. PCR analysis identified E. acervulina, E. maxima, E. tenella, Eimeria necatrix, Eimeria mitis, and Eimeria praecox with variable prevalence across farms and regions. Anticoccidial sensitivity testing of strains of Eimeria isolated from 1 region, no treatment difference (P > 0.05) was observed in final weight (BW), weight gain (BWG) or feed conversion (FCR). For the global resistance index (GI) classified SAL and MET.CLO as good efficacy (85.79 and 85.49, respectively) and DIC as limited efficacy (74.52%). These results demonstrate the ubiquitous nature of Eimeria spp. and identifies the current state of sensitivity to commonly used anticoccidials in a region of poultry importance for Colombia.

Improved method for in vitro secondary amastigogenesis of Trypanosoma cruzi: morphometrical and molecular analysis of intermediate developmental forms.

Trypanosoma cruzi undergoes a biphasic life cycle that consists of four alternate developmental stages. In vitro conditions to obtain a synchronic transformation and efficient rates of pure intermediate forms (IFs), which are indispensable for further biochemical, biological, and molecular studies, have not been reported. In the present study, we established an improved method to obtain IFs from secondary amastigogenesis. During the transformation kinetics, we observed progressive decreases in the size of the parasite body, undulating membrane and flagellum that were concomitant with nucleus remodeling and kinetoplast displacement. In addition, a gradual reduction in parasite movement and acquisition of the amastigote-specific Ssp4 antigen were observed. Therefore, our results showed that the in vitro conditions used obtained large quantities of highly synchronous and pure IFs that were clearly distinguished by morphometrical and molecular analyses. Obtaining these IFs represents the first step towards an understanding of the molecular mechanisms involved in amastigogenesis.

Locomotor mal-performance and gait adaptability deficits in sickle cell mice are associated with vascular and white matter abnormalities and oxidative stress in cerebellum.

Patients with sickle cell disease (SCD) can develop strokes and as a result, present neurologic and neurocognitive deficits. However, recent studies show that even without detectable cerebral parenchymal abnormalities on imaging studies, SCD patients can have significant cognitive and motor dysfunction, which can present as early as during infancy. As the cerebellum plays a pivotal role in motor and non-motor functions including sensorimotor processing and learning, we examined cerebellar behavior in humanized SCD mice using the Erasmus ladder. Homozygous (sickling) mice had significant locomotor malperformance characterized by miscoordination and impaired locomotor gait/stepping pattern adaptability. Conversely, Townes homozygous mice had no overall deficits in motor learning, as they were able to associate a conditioning stimulus (high-pitch warning tone) with the presentation of an obstacle and learned to decrease steptimes thereby increasing speed to avoid it. While these animals had no cerebellar strokes, these locomotor and adaptive gait/stepping patterns deficits were associated with oxidative stress, as well as cerebellar vascular endothelial and white matter abnormalities and blood brain barrier disruption, suggestive of ischemic injury. Taken together, these observations suggest that motor and adaptive locomotor deficits in SCD mice mirror some of those described in SCD patients and that ischemic changes in white matter and vascular endothelium and oxidative stress are biologic correlates of those deficits. These findings point to the cerebellum as an area of the central nervous system that is vulnerable to vascular and white matter injury and support the use of SCD mice for studies of the underlying mechanisms of cerebellar dysfunction in SCD.

[Vaginal metastasis from renal cell carcinoma]. / Metástasis vaginal de carcinoma de células renales.

Vaginal metastases in renal cell carcinoma (RCC) have been reported in rare situations. We present a case of metastatic RCC in a 75-year-old woman, initially presenting with haematuria and vaginal pain. Workup further revealed a renal tumor and a vaginal mass. A nephrectomy and local vaginal excision were performed, leading to the diagnosis of metastatic RCC. This case illustrate the variability in RCC presentation. Also, because vaginal clear cell carcinoma is rare, all such lesions should be considered potentially renal in origin.

[Barriers impeding access to epilepsy surgery: a review of the literature]. / Barreras de acceso a la cirugia de la epilepsia: revision de la bibliografia.

Drug-resistant epilepsy, a chronic condition with long-term consequences can be treated with surgery. The efficacy and safety of surgery for temporal lobe epilepsy have been established through a large number of retrospective and prospective cohort studies and two randomized controlled clinical trials. Despite the excellent outcomes reported after surgery, the literature suggests that this procedure is an underutilized treatment. While evidence is lacking as to why epilepsy surgery is underused, cited reasons include: failure of primary care physicians and neurologists to provide information and identify patients who could be referred for surgery; different levels of technology at various centers, resulting in different candidate selection strategies; the belief that epilepsy surgery is a risky procedure and that it should be only viewed as the last option; patient preference to avoid surgery; parents wanting to wait until their child is old enough to participate in the decision-making process regarding surgery; unwillingness of insurers to cover the expenses associated with presurgical evaluations or lack of insurance; racial and social disparities, among others. In this paper we review the available epidemiological data about lack of utilization of epilepsy surgery.

TITLE: Barreras de acceso a la cirugia de la epilepsia: revision de la bibliografia.La epilepsia farmacorresistente es una condicion cronica con consecuencias a largo plazo que puede ser tratada quirurgicamente. La eficacia y la seguridad de la cirugia de la epilepsia del lobulo temporal se han establecido a traves de un gran numero de estudios de cohorte retrospectivos y prospectivos y dos ensayos clinicos controlados aleatorizados. A pesar de los excelentes resultados comunicados con la cirugia, la bibliografia sugiere que este procedimiento es un tratamiento subutilizado. Aunque no existe evidencia de esto, entre algunos de los motivos descritos se apuntan el fallo de los medicos de atencion primaria y los neurologos en proveer informacion, identificar y remitir a los pacientes a un centro de cirugia; los diferentes niveles de tecnologia en los centros, lo que provoca distintas estrategias de seleccion de los candidatos; la creencia de que la cirugia de la epilepsia es un procedimiento arriesgado que deberia contemplarse solo como ultima opcion; la preferencia del paciente por evitar la cirugia; el deseo de los padres de esperar hasta que sus hijos sean lo suficientemente mayores para participar en el proceso de toma de decisiones; el hecho de que las aseguradoras no cubran los gastos asociados con las evaluaciones prequirurgicas o la carencia de un seguro medico, y la desigualdad racial y social, entre otros. En este articulo se revisan los datos epidemiologicos disponibles en relacion con la falta de acceso a la cirugia de la epilepsia.

Self-consistent-field comparative studies of some nitrosoureas and nitrosamides.

Ab initio (self-consistent-field) calculations are performed in order to obtain information about the most stable conformers of methylnitrosourea, chloroethyl nitrosourea, and their corresponding amides (methylnitrosamide and chloroethylnitrosamide). While nitrosoureas are found to exhibit a Z-conformation, nitrosamides are found to exhibit an E-conformation, a difference which could account for their different stabilities toward in vivo decomposition and which could, as such, influence their carcinostatic activity.

Expression and transcriptional regulation of functionally distinct Bmf isoforms in B-chronic lymphocytic leukemia cells.

Bmf is a BH3-only Bcl-2 family member that is normally sequestered to myosin V motors by binding to the dynein light chain 2 (DLC2). Certain damage signals release Bmf, which then binds prosurvival Bcl-2 proteins and triggers apoptosis. Here, two novel isoforms of human Bmf, Bmf-II and Bmf-III, were identified and cloned from cDNA derived from B-chronic lymphocytic leukemia (B-CLL) cells. Bmf-II and Bmf-III were characterized as two splice variants, lacking the BH3 domain but retaining the DLC2 binding domain. Bmf (here called Bmf-I) expression in HeLa cells induced apoptosis and reduced colony formation in contrast to Bmf-II and Bmf-III, which had no effect on apoptosis and instead increased colony formation. While bmf-I mRNA was expressed in many cell types, expression was higher in B lymphoid cells and bmf-II and bmf-III were mainly detected in B-CLL and normal B cells. bmf-I mRNA was upregulated in normal and leukemic B cells, while bmf-III mRNA was downregulated only in B-CLL cells by serum deprivation. We show that Bmf is regulated by transcriptional activation and alternative splicing and conclude that the relative levels of Bmf isoforms may have a role in regulating growth and survival in B cells and leukemic B-CLL cells.