Chronic Exposure to Arsenic and Fluoride Starting at Gestation Alters Liver Mitochondrial Protein Expression and Induces Early Onset of Liver Fibrosis in Male Mouse Offspring.

The presence of arsenic (As) and fluoride (F-) in drinking water is of concern due to the enormous number of individuals exposed to this condition worldwide. Studies in cultured cells and animal models have shown that As- or F-induced hepatotoxicity is primarily associated with redox disturbance and altered mitochondrial homeostasis. To explore the hepatotoxic effects of chronic combined exposure to As and F- in drinking water, pregnant CD-1 mice were exposed to 2 mg/L As (sodium arsenite) and/or 25 mg/L F- (sodium fluoride). The male offspring continued the exposure treatment up to 30 (P30) or 90 (P90) postnatal days. GSH levels, cysteine synthesis enzyme activities, and cysteine transporter levels were investigated in liver homogenates, as well as the expression of biomarkers of ferroptosis and mitochondrial biogenesis-related proteins. Serum transaminase levels and Hematoxylin-Eosin and Masson trichrome-stained liver tissue slices were examined. Combined exposure at P30 significantly reduced GSH levels and the mitochondrial transcription factor A (TFAM) expression while increasing lipid peroxidation, free Fe 2+, p53 expression, and serum ALT activity. At P90, the upregulation of cysteine uptake and synthesis was associated with a recovery of GSH levels. Nevertheless, the downregulation of TFAM continued and was now associated with a downstream inhibition of the expression of MT-CO2 and reduced levels of mtDNA and fibrotic liver damage. Our experimental approach using human-relevant doses gives evidence of the increased risk for early liver damage associated with elevated levels of As and F- in the diet during intrauterine and postnatal period.

Chronic exposure to inorganic arsenic and fluoride induces redox imbalance, inhibits the transsulfuration pathway, and alters glutamate receptor expression in the brain, resulting in memory impairment in adult male mouse offspring.

Exposure to toxic elements in drinking water, such as arsenic (As) and fluoride (F), starts at gestation and has been associated with memory and learning deficits in children. Studies in which rodents underwent mechanistic single exposure to As or F showed that the neurotoxic effects are associated with their capacity to disrupt redox balance, mainly by diminishing glutathione (GSH) levels, altering glutamate disposal, and altering glutamate receptor expression, which disrupts synaptic transmission. Elevated levels of As and F are common in groundwater worldwide. To explore the neurotoxicity of chronic exposure to As and F in drinking water, pregnant CD-1 mice were exposed to 2 mg/L As (sodium arsenite) and 25 mg/L F (sodium fluoride) alone or in combination. The male litter continued to receive exposure up to 30 or 90 days after birth. The effects of chronic exposure on GSH levels, transsulfuration pathway enzymatic activity, expression of cysteine/cystine transporters, glutamate transporters, and ionotropic glutamate receptor subunits as well as behavioral performance in the object recognition memory task were assessed. Combined exposure resulted in a significant reduction in GSH levels in the cortex and hippocampus at different times, decreased transsulfuration pathway enzyme activity, as well as diminished xCT protein expression. Altered glutamate receptor expression in the cortex and hippocampus and decreased transaminase enzyme activity were observed. These molecular alterations were associated with memory impairment in the object recognition task, which relies on these brain regions.

Clinical characteristics and functional outcome of pediatric ocular trauma in a third level reference hospital in Guadalajara, Mexico.

BACKGROUND: Ocular trauma is one of the leading causes of decreased visual acuity and monocular blindness in the pediatric population. Since its occurrence is potentially preventable, it is essential to understand its demographic characteristics and risk factors to alert and implement prevention and health promotion programs. METHODS: We conducted a retrospective study in which we reviewed 187 clinical records of patients ≤ 15 years old with the diagnosis of severe ocular trauma admitted in 2017 to the Hospital Civil de Guadalajara. We analyzed demographic variables, circumstances of the event, type of treatment, and the evolution of visual acuity and complications. RESULTS: In total, 187 patients and 188 eyes were included; the average age was 6.99 ± 4.1 years. Children of 2 to 5 years of age (41%) were the most affected, and a higher occurrence was observed in males (73%). Open ocular trauma was the most common type of injury (72.7%) caused by sharp objects (45.4%). Most injuries occurred at home (78.1%), without adult supervision (48.1%), and during leisure time (74.9%). Most events were accidental (80.4%), although 12.3% were direct aggression. Surgery was required in 179 patients, in whom corneal injury repair (43.2%) was the most commonly used procedure. Final visual acuity was quantified in 132 eyes, and visual acuity < 20/200 was found in 18.1%. Loss of 4.2% of the eyeballs was recorded. CONCLUSIONS: The highest proportion of cases was identified in male patients ≤5 years old, unsupervised by an adult. Many eye injuries are preventable, so it is necessary to implement socio-educational programs in alliance with pediatric organizations that alert the severity of the problem and promote safe environments.

INTRODUCCIÓN: El trauma ocular es una de las principales causas de disminución de la agudeza visual y de ceguera monocular en la población pediátrica. Su ocurrencia es potencialmente prevenible, por lo que es importante entender sus características demográficas y riesgos para alertar e implementar programas enfocados hacia la prevención y la promoción de la salud. MÉTODOS: Estudio retrospectivo en el que se analizaron 187 expedientes de pacientes ≤ 15 años con diagnóstico de trauma ocular grave ingresados en 2017 al Hospital Civil de Guadalajara. Se analizaron variables demográficas, circunstancias del evento y tipo de tratamiento, así como la evolución de la agudeza visual y las complicaciones. RESULTADOS: Se incluyeron 187 pacientes y 188 ojos; el promedio de edad en el momento del trauma fue de 6.99 ± 4.1 años. Los niños de 2-5 años (41%) fueron los más afectados y se observó una mayor ocurrencia en el sexo masculino (73%). El trauma ocular abierto fue el tipo de lesión más común (72.7%), causado por objetos punzantes (45.4%). La mayoría de las lesiones ocurrieron en casa (78.1%), sin supervisión de un adulto (48.1%) y durante el tiempo libre (74.9%). La mayoría de los sucesos fueron accidentales (80.4%), aunque el 12.3% fue por agresiones directas. Se requirió cirugía en 179 pacientes, en quienes la reparación de lesión corneal (43.2%) fue el procedimiento más utilizado. La agudeza visual final se cuantificó en 132 ojos y se encontró < 20/200 en el 18.1%. Se registró la pérdida del 4.2% de los globos oculares. CONCLUSIONES: La proporción más alta de casos se identificó en pacientes de sexo masculino ≤ 5 años, que se encontraban sin supervisión. Una gran proporción de las lesiones oculares son prevenibles, por lo que es necesario implementar programas educativos sociales en coordinación con organizaciones pediátricas que alerten de la gravedad del problema y promuevan entornos seguros.

Extracranial midline defects in a patient with craniofrontonasal syndrome with a novel EFNB1 mutation.

We report a female patient with craniofrontonasal syndrome (CFNS) who in addition showed other cranial and extracranial midline defects including partial corpus callosum agenesis, ocular melanocytosis, pigmentary glaucoma, duplex collecting system, uterus didelphys, and septate vagina. She was found to have a novel pathogenic variant in exon 5 of EFNB1, c.646G>T (p.Glu216*) predicted to cause premature protein truncation. From our review, we found at least 39 published CFNS patients with extracranial midline defects, comprising congenital diaphragmatic hernia, congenital heart defects, umbilical hernia, hypospadias, and less frequently, sacrococcygeal teratomas, and internal genital anomalies in females. These findings support that the EFNB1 mutations have systemic consequences disrupting morphogenetic events at the extracranial midline. Though these are not rigorously included as midline defects, we found at least 10 CFNS patients with congenital anomalies of the kidney and urinary tract, all females. Additionally, uterus didelphys and ocular melanocytosis observed in our patient are proposed also as a previously unreported EFNB1-related midline defects. In addition, this case may be useful for considering the intentional search for genitourinary anomalies in future patients with CFNS, which will be helpful to define their frequency in this entity.

Oropharyngeal dysphagia in early stages of myotonic dystrophy type 1.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized mainly by skeletal muscle alterations. Although oropharyngeal dysphagia is a prominent clinical feature of DM1, it remains poorly studied in its early disease stages. METHODS: Dysphagia was investigated in 11 presymptomatic DM1 carriers, 14 patients with DM1 and 12 age-matched healthy controls, by using fiberoptic endoscopic evaluation of swallowing (FEES) and clinical scores. RESULTS: Scores for the FEES variables, delayed pharyngeal reflex, posterior pooling, and postswallow residue were significantly greater in patients with DM1 and in presymptomatic DM1 carriers than in healthy controls (P < 0.05); oropharyngeal dysfunction was more severe in patients than in presymptomatic carriers. Penetration/aspiration was found altered exclusively in patients with DM1 (P < 0.05). DISCUSSION: Swallowing dysfunction occurs in presymptomatic DM1 carriers. Timely diagnosis of dysphagia in preclinical stages of the disease will aid in the timely management of presymptomatic carriers, potentially preventing medical complications. Muscle Nerve, 2019.

Clival Chondroid Chordoma: A Case Report and Review of the Literature.

Chordomas are rare, slow-growing, and locally aggressive malignant neoplasms derived from primitive notochord remnants. The chondroid variety represents 14% of all chordomas mainly developing in the spheno-occipital region and presenting between the third and fifth decades of life. When developing intracranially, symptoms can range from headaches and neck pain to cranial nerve neuropathies and facial numbness. We illustrate a case of an adolescent woman who presented with excruciating facial pain, otalgia, decreased visual acuity, quadriparesis, headache, nausea, and dysphagia. Radiological studies revealed a large heterogeneous mass in the spheno-occipital region with clivus destruction. Biopsy and histopathology confirmed the diagnosis. Proper identification with prompt surgical resection and adjuvant radiotherapy remains critical to prevent complications.

Evaluation of kidney injury biomarkers in an adult Mexican population environmentally exposed to fluoride and low arsenic levels.

Fluoride (F) is a toxicant widely distributed in the environment. Experimental studies have shown kidney toxicity from F exposure. However, co-exposure to arsenic (As) has not been considered, and epidemiological information remains limited. We evaluated the association between F exposure and urinary kidney injury biomarkers and assessed As co-exposure interactions. A cross-sectional study was conducted in 239 adults (18-77 years old) from three communities in Chihuahua, Mexico. Exposure to F was assessed in urine and drinking water, and As in urine samples. We evaluated the urinary concentrations of albumin (ALB), cystatin-C (Cys-C), kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN), and trefoil factor 3 (TFF-3). The estimated glomerular filtration rate (eGFR) was calculated using serum creatinine (Creat) levels. We observed a positive correlation between water and urine F concentrations (ρ = 0.7419, p < 0.0001), with median values of 1.5 mg/L and 2 µg/mL, respectively, suggesting that drinking water was the main source of F exposure. The geometric mean of urinary As was 18.55 ng/mL, approximately 39% of the urine samples had As concentrations above the human biomonitoring value (15 ng/mL). Multiple linear regression models demonstrated a positive association between urinary F and ALB (ß = 0.56, p < 0.001), Cys-C (ß = 0.022, p = 0.001), KIM-1 (ß = 0.048, p = 0.008), OPN (ß = 0.38, p = 0.041), and eGFR (ß = 0.49, p = 0.03); however, CLU (ß = 0.07, p = 0.100) and TFF-3 (ß = 1.14, p = 0.115) did not show significant associations. No interaction with As exposure was observed. In conclusion, F exposure was related to the urinary excretion of early kidney injury biomarkers, supporting the hypothesis of the nephrotoxic role of F exposure.

Mieloma múltiplo em cão com apresentação clínica atípica de paralisia facial bilateral: relato de caso / Multiple Myeloma in dog with atypical clinical presentation of bilateral facial paralysis: case report

Objetivou-se com o presente trabalho relatar um caso de mieloma múltiplo (MM) em uma cadela com apresentação clínica atípica de rigidez da musculatura facial. Foram realizados hemogramas seriados, exames bioquímicos, sumário de urina, sorologia para leishmaniose, radiografias de crânio, citologia de medula óssea e eletroforese de proteínas séricas. O infiltrado plasmocitário em medula óssea >20%, a gamopatia monoclonal e as lesões compatíveis com lise óssea, observados no mielograma, eletroforese de proteínas e exame radiográfico, respectivamente, foram determinantes para conclusão diagnóstica de MM. A doença pode ter uma apresentação clínica variável em cães e representar um desafio ao diagnóstico na clínica de animais de companhia, principalmente em áreas endêmicas de doenças infecciosas que se manifestam com apresentações clínicas e laboratoriais semelhantes.(AU)

This paper reports a case of multiple myeloma (MM) in a bitch with atypical clinical presentation of rigidity of the facial muscles. Hemogram, biochemical tests, urinalysis, serology for leishmaniasis, skull radiography, bone marrow cytology and serum protein electrophoresis were performed. The plasma cell infiltration in bone marrow was >20 %, the monoclonal gammopathy and lesions compatible with bone lysis observed in the myelogram, protein electrophoresis and radiographic examination respectively, were decisive for diagnostic conclusion of MM. The disease may have a variable clinical presentation in dogs and pose a challenge for diagnosis in the pet clinic, especially in endemic areas of infectious diseases that present with similar clinical and laboratory presentations.(AU)

UV-B radiation reduces in vitro germination of Metarhizium anisopliae s.l. but does not affect virulence in fungus-treated Aedes aegypti adults and development on dead mosquitoes.

AIMS: Control of diurnal Aedes aegypti with mycoinsecticides should consider the exposure of fungus-treated adults to sunlight, and especially to UV-B radiation that might affect activity of conidia applied on the mosquito's surface. METHODS AND RESULTS: Germination of Metarhizium anisopliae s.l. IP 46 conidia on SDAY medium was not affected at the lowest level of radiation with UV-B, 0·69 kJ m-2 , but was retarded and reduced at higher 2·075 and 4·15 kJ m-2 , and completely inhibited at ≥8·3 kJ m-2 . In contrast, germination of conidia applied onto fibreglass nettings and exposed from 0 to 16·6 kJ m-2 did not differ significantly among levels of irradiance exposure and the controls. There was also no significant impact of UV-B up to 16·6 kJ m-2 on the adulticidal activity of IP 46 and on the subsequent conidiogenesis on cadavers. The Quaite-weighted UV-B irradiance in the laboratory (1152 mW m-2 ) was higher than the natural sunlight irradiance observed in the city of Goiânia in Central Brazil on midday (706 mW m-2 in August to 911 mW m-2 in October 2015). CONCLUSIONS: UV-B does not impair the activity of IP 46 conidia applied previously to radiation on A. aegypti adults. SIGNIFICANCE AND IMPACT OF THE STUDY: Findings contribute to a better understanding of the effectiveness of M. anisopliae against day-active A. aegypti and its potential for biological mosquito control.

Case series of infants presenting with end stage retinopathy of prematurity to two tertiary eye care facilities in Mexico: underlying reasons for late presentation.

To describe the characteristics of infants with bilateral Stage 4b or 5 ROP (i.e. with subtotal or total retinal detachment) who presented to eye departments in two major cities in Mexico, to identify reasons why they may have become blind in order to recommend how programs could be improved. A large case-series of infants with Stage 4b or 5 ROP in both eyes confirmed by ultrasound who attended the ROP Clinic, Hospital Civil de Guadalajara from September 2010 to November 2012, and the Department of Ophthalmology, Hospital Infantil de Mexico Federico Gomez from December 2011 to December 2012 were identified from the diagnostic databases of each hospital. Mothers of infants in Guadalajara had a telephone interview. 89/94 eligible infants were included in the study, 48 in Guadalajara and 41 in Mexico City. Cases came from 22 of the 32 states in Mexico. Half of the infants attending Guadalajara 24/48 (50 %) had been cared for in NICUs without ROP screening programs and were not examined. Among the 24 infants cared for in NICUs with ROP programs, 7/24 (29.1 %) mothers reported that their infant had not been examined while in the NICU, and a further 9/24 (37.5 %) were either not referred for screening after discharge or they did not attend. Two infants had failed laser treatment. Strategies and resources to prevent end stage ROP have not been firmly established in Mexico. There is an urgent need to expand the coverage and quality of ROP programs, to ensure that existing screening guidelines are better adhered to, and to improve communication with parents.

Aislación y caracterización de células madre mesenquimales provenientes de pulpa y folículo dentario humano / Isolation and characterization of mesenchymal stem cells from human dental pulp and follicle

Recientemente se ha descubierto que diversos tejidos dentales son fuente importante de Células Madre Mesenquimales (CMM). En la cavidad oral podemos encontrar CMM en la pulpa, en el folículo dental, papila y en la encía entre otros lugares. Varios estudios avalan el extenso potencial terapéutico de las CMM en terapias de regeneración. El objetivo de este estudio es aislar, cultivar células madres mesenquimales de pulpa y folículo dental humano, caracterizar su inmunofenotipo y su potencial de diferenciación a linaje osteogénico, condrogénico y osteogénico. Se cultivaron células de pulpa y folículo dental de terceros molares de dientes permanentes jóvenes humanos. Los cultivos de CMM fueron monitoreados por microscopia óptica, las células se inmunotipificaron por citometría de flujo. Posteriormente se evaluó su capacidad de diferenciaron a los tres linajes mencionados. En estas condiciones experimentales se comprobó que las células aisladas y cultivadas de pulpa y folículo dental correspondían a células madre mesenquimales humanas, siendo éstas últimas más fáciles de obtener y proliferar. Las CMM de folículo dental poseen mayor potencial de crecimiento y capacidad de diferenciación en comparación a las CMM de pulpa dental, probablemente debido a su estado evolutivo más inmaduro.

It was recently discovered that dental tissues are important sources of mesenchymal stem cells (MSCs). In the oral cavity MSCs can be found in the pulp, dental follicle, apical papilla and gingival tissue, among others. Many studies support the therapeutic potential of MSCs in regenerative therapies. The objective of this study was to isolate and culture mesenchymal stem cells from human dental pulp and follicle, and to characterize their immunophenotype and differentiation potential to adipogenic, chondrogenic and osteogenic lineages. Oral cavity stem cells were cultured from pulp and dental follicle of wisdom teeth from young permanent teeth. Immunotypification of MSCs was performed by flow cytometry and cultures were evaluated for their ability to differentiate into the three lineages mentioned. Our results corroborate that cultured oral MSC cells isolated from pulp and dental follicle were mesenchymal in origin, being the latter more easy to obtain. Dental follicle MSCs have greater growth potential and differentiation capacity compared to dental pulp MSCs, probably due to their more immature developmental state.

Is there a benefit to adding rituximab to CHOP in the overall survival of patients with B-cell non-Hodgkin's lymphoma in a developing country?

Rituximab (R) has changed the prognosis of patients with non-Hodgkin's lymphoma (NHL) in developed countries, but its role has not been analyzed in underprivileged circumstances. One hundred and two patients with NHL treated in a developing country were analyzed: 28 patients with follicular lymphoma (FL) and 74 with diffuse large B-cell lymphoma (DLCL). Patients were treated upfront with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or R-CHOP; the decision to employ R depending solely on the ability of patients to defray it. In DLCL, 42 were given CHOP and 32 R-CHOP, whereas in FL, 19 were given CHOP and 9 R-CHOP. The impact of the addition of R was found to be clearer in FL than in DLCL. In patients with DLCL, the overall survival (OS) was 87% at 80 months for those treated with R-CHOP and 84% at 145 months for those treated with CHOP (not significant). In patients with FL, the OS was 89% at 88 months for those treated with R-CHOP and 71% at 92 months for those treated with CHOP (P = 0··05). In a multivariate analysis, other variables which were identified to be associated with the OS were IPI and number of cycles in DLCL. It is concluded that R produced a mild positive impact in the OS of patients with FL, but not in those with DLCL. Since the addition of R results in a 36-fold increase in treatment costs, these observations may be important to decide therapeutic approaches in NHL patients living in underprivileged circumstances.

Treatment of hairy cell leukemia: long-term results in a developing country.

Twenty-nine consecutive patients with hairy cell leukemia (HCL) were treated in two institutions with interferon (IFN, n = 18) or cladribine (n = 11), between July 1987 and May 2011. Median age was 62 (range 29-83) years; there were 21 males and 8 females. Seven of the 18 patients in the IFN group (39%) achieved a complete remission (CR), whereas all the patients in the 2-CDA group entered a CR. Three patients in the 2-CDA group relapsed and needed an additional course of the drug, 2, 3 and 6 years after the initial one. The median overall survival (OS) of the whole group has not been reached, being above 217 months, the 217-month OS being 91%. The survival of patients treated with either IFN or 2-CDA was not statistically different (94% OS at 217 months versus 91% OS at 133 months, respectively). The data that we present here suggest that treatment of HCL with either 2-CDA or IFN is equally effective; treatment costs with IFN are substantially lower than those of the purine analog.

Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy

Abstract The reduction of skeletal muscle loss in pathological states, such as muscle disuse, has considerable effects in terms of rehabilitation and quality of life. Since there is no currently effective and safe treatment available for skeletal muscle atrophy, the search for new alternatives is necessary. Resistance exercise (RE) seems to be an important tool in the treatment of disuse-induced skeletal muscle atrophy by promoting positive functional (strength and power) and structural (hypertrophy and phenotypic changes) adaptive responses. Human and animal studies using different types of resistance exercise (flywheel, vascular occlusion, dynamic, isometric, and eccentric) have obtained results of great importance. However, since RE is a complex phenomenon, lack of strict control of its variables (volume, frequency, intensity, muscle action, rest intervals) limits the interpretation of the impact of the manipulation on skeletal muscle remodeling and function under disuse. The aim of this review is to critically describe the functional and morphological role of resistance exercise in disuse-induced skeletal muscle atrophy with emphasis on the principles of training.

Dose-dependent urinary phenotype of inorganic arsenic methylation in mice with a focus on trivalent methylated metabolites.

Inorganic arsenic (iAs) exposure has been associated with the increased risk of various forms of cancer and of non-cancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. However, in vivo research involving the production of MAsIII and DMAsIII remains an area of ongoing investigation and debate. The results of metabolic and toxicity studies using mice have been entirely applicable to other species including humans. The goal of this study was to investigate the phenotype for the trivalent and pentavalent arsenic metabolites in relation to arsenite dose via immediate analysis of fresh urine samples, while preventing the oxidation of unstable methylated AsIII-containing metabolites. Female mice (C57BL/6) received sodium arsenite by gavage at doses of 0, 3, 6 or 10 mg As/kg/day for 9 days, after which trivalent methylated arsenicals were detected in 100% of urine samples; these arsenicals were not detected in the urine of control mice. The amount of DMAsIII detected in urine depended on the dose of arsenite administered and was determined to be 50.2%, 31.4% and 16.5% of the total urinary arsenic in mice exposed to 3, 6, or 10 mg/kg/day, respectively. This relationship is consistent with the hypothesis of inhibition or saturation of iAs methylation. Understanding the in vivo production of MAsIII and DMAsIII in mice exposed to iAs could aid in developing a biologically based dose-response model for iAs.

Conocimientos y actitudes sobre educación vial: predictores de riesgo en escolares de educación primaria, sus madres y profesores: Ica-Perú / Knowledge and attitudes about road safety education: predictors of risk. In primary school, their mothers and teachers: Ica - Perú

Estudio descriptivo, prospectivo, transversal. Objetivo: Determinar el nivel de conocimientos y actitudes sobre Educación Vial, en escolares de Educación Primaria, madres y profesores, como predictores de riesgo de accidentes de tránsito. Métodos. Se seleccionaron aleatoriamente: 4/14 distritos de la Provincia de lea, 13 colegios y 175 alumnos del segundo al sexto grado, aplicándoseles cuestionario ad-hoc, así como a sus madres (90) y profesores (104). Directores de los colegios, fueron entrevistados sobre actividades de educación vial. La validez y confiabilidad del cuestionario, se realizó en base a juicios de expertos, prueba piloto y prueba alfa de Crombach (.762). Para el análisis estadístico se utilizó SPSS 14, determinándose: frecuencias, porcentajes y análisis factorial (pruebas KMO y de Bartlett). Resultados: El análisis factorial reveló: en escolares, conocimientos y actitudes inadecuadas sobre señales de tránsito (.760), tendencia a cruzar por zona no peatonal (.763) y placer por la velocidad (.600); en madres y profesores, puntuaciones más significativas. Los Directores informaron no existencia de curso específico en el plan de estudio. Conclusiones: Los predictores de riesgo más relevantes se relacionan a: no respetar señales de tránsito, no utilizar zonas peatonales y placer por la velocidad. Recomendándose programas de educación vial a la comunidad en su conjunto.

In this prospective, cross-sectional, descriptive, research. Objective: To determine level ofknowledge and attitudes about road education in primary schoolchildren, mothers and teachers, as predictors of risk of traffic accidents. Methods: There were randomly selected: 4/14 districs ofthe province ofIca, 13 schools and 175 students from second to sixth grade, applying to them ad-hoc questionnaire, and their mothers (90) and teachers (104). Directors of schools, were interviewed about road safety education activities. The validity and reliability ofthe questionnaire were made based on expert opinions, pilot test and Crombach alpha test (.762). The statistical analysis was used SPSS14, determining: frequencies, percentages and factor analysis (KMO and Bartlett test). Results: The factor anlysis showed: in schoolchilds, inadequate knowledge and attitudes about traffic signs (.760), a tendency to cross by no pedestrian zone (.763) and enjoy the speed (.600), in mothers and teachers, scores more significant. Directors reported no existence of specific course in the curriculum. Conclusions: The predictors of risk are related to the most important: do not respect traffic signals, do not use pedestrian gones and enjoy the speed. Recommended driver education programs to the community as a whole.

Danazol as first-line therapy for aplastic anemia.

Immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) plus cyclosporine A (CsA) is the standard treatment for aplastic anemia (AA) patients not eligible for allogeneic hematopoietic stem cell transplantation (HSCT). In the absence of ATG + CsA, androgens continue to be a treatment option. We documented the clinical evolution of AA patients treated with danazol instead of ATG + CsA. AA patients lacking both, human leukocyte antigen-matched donor and access to IST, were treated with danazol and modern support therapy and compared with those receiving a HSCT. Overall survival (OS), response rates, and death risk odds were calculated. Fifty AA patients were studied. Thirteen received a HSCT and 37 danazol and support therapy. Median daily dose of danazol was 400 mg (300 to 600 mg), administered during a median of 12 months. Five-year OS was higher for patients receiving HSCT (92%) compared to the danazol group (41%) (P = 0.001). Overall response rate was 46% (17/37) in the danazol-treated group and the median time to initial response was 3 months (1-27). Tendency to achieve remission was similar among severity groups (P = 0.094). The only adverse side effect recorded on the danazol group was an episode of gastrointestinal bleeding. No patient treated with danazol suffered clonal evolution of his/her disease. Although ATG plus CsA is the therapy of choice for AA patients without a donor when neither HSCT nor IST is available, danazol remains an acceptable therapeutic option for AA patients.

Arsenic species, AS3MT amount, and AS3MT gene expression in different brain regions of mouse exposed to arsenite.

Human exposure to inorganic arsenic (iAs) has been associated with cancer and serious injury to various internal organs, as well as peripheral neuropathy, endocrine disruption and diverse effects in the central nervous system (CNS). Using rodent models, it is possible to demonstrate As accumulation in the brain that leads to defects in operant learning, behavioral changes, and affect pituitary gonadotrophins. iAs biomethylation in the CNS is a significant process, yielding products that are more reactive and toxic than the parent compound. Mice received 2.5, 5, and 10 mg/kg/day sodium arsenite orally for 9 days. We investigated the distribution of iAs and its metabolites as well as the mRNA and protein expression of arsenic (III) methyltransferase (AS3MT), which encodes the key enzyme in iAs metabolism, in the cerebral cortex, hippocampus, striatum, mesencephalon, thalamus, cerebellum, hypothalamus, pons, medulla oblongata, and pituitary of mouse brain. Our findings show that methylated As metabolites are present in all brain regions studied suggesting that AS3MT is ubiquitously expressed in the brain and it is not inducible by dose of arsenite. There is also a dose-related accumulation of As species in all brain regions, with the highest accumulation observed in the pituitary. The higher distribution of arsenicals in pituitary can help to explain the neuroendocrine effects associated with iAs exposure.