Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers.

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

Flexural Properties of Lattices Fabricated with Planar and Curved Layered Fused Filament Fabrication.

The use of curved layers in fused filament fabrication could lead to various advantages in surface finishing and mechanical properties. Here, the influence of three different structural and manufacturing parameters (volume fraction, raster arrangement, and the use of curved or planar layers) on the mechanical properties of lattice structures under three-point bending is studied. Two different raster arrangements were considered, i.e., those with rasters at planes parallel to the principal axes of the samples and those diagonally arranged, all at four different volume fractions. All different samples were additively manufactured using planar and curved layers. Samples were further dimensionally inspected to refine the computational models before their analysis via finite element simulations. The linear elastic region of the load-displacement curves was further analyzed numerically via finite element models. Predictions with finite element models resulted in good agreement with errors below 10%. Samples with diagonal rasters were 70% softer than those parallel to the principal axes.

Effects of a Light Crude Oil Spill on a Tropical Coastal Phytoplankton Community.

Oiling scenarios following spills vary in concentration and usually can affect large coastal areas. Consequently, this research evaluated different crude oil concentrations (10, 40, and 80 mg L-1) on the nearshore phytoplanktonic community in the southern Gulf of Mexico. This experiment was carried out for ten days using eight units of 2500 L each; factors monitored included shifts in phytoplankton composition, physicochemical parameters and the culturable bacterial abundance of heterotrophic and hydrocarbonoclastic groups. The temperature, salinity, and nutrient concentrations measured were within the ranges previously reported for Yucatan Peninsula waters. The total hydrocarbon concentration (TPH) in the control at T0 indicated the presence of hydrocarbons (PAHs 0.80 µg L-1, aliphatics 7.83 µg L-1 and UCM 184.09 µg L-1). At T0, the phytoplankton community showed a similar assemblage structure and composition in all treatments. At T10, the community composition remained heterogeneous in the control, in agreement with previous reports for the area. However, for oiled treatments, Bacillariophyceae dominated at T10. Hydrocarbonoclastic bacteria were associated with oiled treatments throughout the experiment, while heterotrophic bacteria were associated with control conditions. Our results agreed with previous works at the taxonomic level showing the presence of Bacillariophyceae and Dinophyceae in oil-related treatments, where these groups showed the major interactions in co-occurrence networks. In contrast, Chlorophyceae showed the key node in the co-occurrence network for the control. This study aims to contribute to knowledge on phytoplankton community shifts during a crude oil spill in subtropical oligotrophic regions.

Changes in the neutrophil to lymphocyte ratio as predictors of outcome in pediatric patients with central nervous system tumors undergoing surgical resection.

BACKGROUND: Changes in neutrophil to lymphocyte ratio (ΔNLR) have been used as a clinical tool for stratification and prognosis of patients with solid tumors, there is scarce evidence of their clinical relevance in patients with tumors of the central nervous system who have also undergone surgical resection. OBJECTIVE: Determine if (ΔNLR) are associated with poor response to treatment and worse prognosis in pediatric patients with central nervous system tumors (CNST) who underwent surgical resection. METHODS: We performed a retrospective cohort study; demographic, clinical, and hematological variables were evaluated, Kaplan-Meier survival curves and Cox proportional hazards regression model were performed to evaluate prognosis. RESULTS: The ΔNLR cutoff value obtained through the third interquartile range was 4.30; The probability of survival and complete response to treatment was different between patients with high ΔNLR when compared to patients with low ΔNLR (p= 0.013, p=≪ 0.001, respectively). A high ΔNLR behaved as an independent predictor of worse Overall Survival (HR 2,297; 95% CI: 1,075-4.908, p= 0.032). CONCLUSION: An elevated ΔNLR was a predictor of poor response to treatment and a prognostic factor for worse Overall Survival in pediatric patients with CNST undergoing surgical resection.

Genetic polymorphism of CYP3A4 is associated with poor response to ifosfamide treatment in children with solid embryonic tumors.

INTRODUCTION: The CYP450 complex participates in the metabolism of ifosfamide, an antineoplastic drug used to treat solid tumors. CYP450 genes contain several single nucleotide polymorphisms (SNPs) that confer different activity towards the enzyme. The aim of our study was to analyze gene frequencies of allelic variants and their association with ifosfamide blood levels and patient prognosis. MATERIAL AND METHODS: 148 DNA samples from children were analyzed. Genotyping was performed by real-time PCR with TaqMan probes and ifosfamide levels were determined in dried blood drop by UPLCMS/MS. RESULTS: Ifosfamide levels increased according to the genotype, and patients with the variant rs1799853 in CYP2C9 genotype CC had lower levels of ifosfamide (median = 1.8 µmol/l, Q25 0.9-Q75 4.6) compared with patients with genotype TT + CT (median = 2.8 µmol/l, Q25 1.9-Q75 5.1), p < 0.001. In the case of the rs2740574 variant in the CYP3A4 gene, patients with normal genotype (TT) presented median = 1.4 µmol/l, (Q25 0.7-Q75 2.7), while patients with the CC + TC genotype had higher levels of ifosfamide (median = 2.0 µmol/l, Q25 1.0-Q75 4.3), p = 0.024. In addition, patients with CC + CT genotype of this variant had a higher risk of non-response to treatment compared to patients with TT genotype (RR = 1.3, 95% CI: 1.07-1.59, p = 0.03). CONCLUSIONS: Polymorphisms in CYP2C9 and CYP3A4 genes are associated with high levels of ifosfamide. In addition, the polymorphism rs2740574 in CYP3A4 was associated with a worse therapeutic response.

Evaluation of a Fast Test Based on Biometric Signals to Assess Mental Fatigue at the Workplace-A Pilot Study.

Non-pathological mental fatigue is a recurring, but undesirable condition among people in the fields of office work, industry, and education. This type of mental fatigue can often lead to negative outcomes, such as performance reduction and cognitive impairment in education; loss of focus and burnout syndrome in office work; and accidents leading to injuries or death in the transportation and manufacturing industries. Reliable mental fatigue assessment tools are promising in the improvement of performance, mental health and safety of students and workers, and at the same time, in the reduction of risks, accidents and the associated economic loss (e.g., medical fees and equipment reparations). The analysis of biometric (brain, cardiac, skin conductance) signals has proven to be effective in discerning different stages of mental fatigue; however, many of the reported studies in the literature involve the use of long fatigue-inducing tests and subject-specific models in their methodologies. Recent trends in the modeling of mental fatigue suggest the usage of non subject-specific (general) classifiers and a time reduction of calibration procedures and experimental setups. In this study, the evaluation of a fast and short-calibration mental fatigue assessment tool based on biometric signals and inter-subject modeling, using multiple linear regression, is presented. The proposed tool does not require fatigue-inducing tests, which allows fast setup and implementation. Electroencephalography, photopletismography, electrodermal activity, and skin temperature from 17 subjects were recorded, using an OpenBCI helmet and an Empatica E4 wristband. Correlations to self-reported mental fatigue levels (using the fatigue assessment scale) were calculated to find the best mental fatigue predictors. Three-class mental fatigue models were evaluated, and the best model obtained an accuracy of 88% using three features, ß/θ (C3), and the α/θ (O2 and C3) ratios, from one minute of electroencephalography measurements. The results from this pilot study show the feasibility and potential of short-calibration procedures and inter-subject classifiers in mental fatigue modeling, and will contribute to the use of wearable devices for the development of tools oriented to the well-being of workers and students, and also in daily living activities.

Relationship between paralytic shellfish toxin content and sxtA gene copy number in different growth phases of Gymnodinium catenatum (Dinophyceae).

Paralytic shellfish toxin (PST) content in the dinoflagellate Gymnodinium catenatum changes with culture age, with a higher toxin concentration in the logarithmic phase that decreases when the culture ages. The gene copy number (GCN) of domains sxtA1 and sxtA4 was higher in the lag and stationary phase, and lag phase, respectively. No relationship was found between the GCN of the domains sxtA4 and sxtA1 with the PST content in G. catenatum.

Analysis of CYP450 gene allelic variants can predict ifosfamide toxicity in Mexican paediatric patients.

Context: Ifosfamide (IFA) is an effective antineoplastic for solid tumours in children, although it is associated with high levels of systemic toxicity and causes death in some cases. Objective: The aim of this study was to determine whether the presence of certain allelic variants of genes CYP2B6, CYP2C9, CYP3A4 and CYP3A5 increases the risk of toxicity in children with solid tumours treated with ifosfamide.Materials and methods: A total of 131 DNA samples were genotyped by real-time polymerase chain reaction (RT-PCR) using TaqMan probes. Toxicity was assessed using WHO criteria, and survival analysis was performed using Kaplan-Meier curves.Results: The rs3745274 allelic variant in CYP2B6 was associated with haematological toxicity, affecting neutrophils; CYP3A4 variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the CYP3A5 gene variant rs776746 was found to affect haemoglobin.Conclusions: Our results show that allelic variants rs3745274 (CYP2B6), rs2740574 (CYP34) and rs776746 (CYP3A5) increase the risk for high haematological toxicity.Clinical trial registration: 068/2013.

Characterization of the Mechanical Properties of FFF Structures and Materials: A Review on the Experimental, Computational and Theoretical Approaches.

The increase in accessibility of fused filament fabrication (FFF) machines has inspired the scientific community to work towards the understanding of the structural performance of components fabricated with this technology. Numerous attempts to characterize and to estimate the mechanical properties of structures fabricated with FFF have been reported in the literature. Experimental characterization of printed components has been reported extensively. However, few attempts have been made to predict properties of printed structures with computational models, and a lot less work with analytical approximations. As a result, a thorough review of reported experimental characterization and predictive models is presented with the aim of summarizing applicability and limitations of those approaches. Finally, recommendations on practices for characterizing printed materials are given and areas that deserve further research are proposed.

Early synergistic interactions between the HPV16­E7 oncoprotein and 17ß-oestradiol for repressing the expression of Granzyme B in a cervical cancer model.

Although high-risk human papillomavirus (HR­HPV) infection has a prominent role in the aetiology of cervical cancer (CC), sex steroid hormones may also be involved in this process; however, the cooperation between oestrogen and HR­HPV in the early stages of cervical carcinogenesis is poorly understood. Since 17ß-oestradiol (E2) and the HPV type 16­E7 oncoprotein induce CC in transgenic mice, a microarray analysis was performed in the present study to generate global gene expression profiles from 2­month­old FVB (non­transgenic) and K14E7 (transgenic) mice who were left untreated or were treated for 1 month with E2. Upregulation of cancer-related genes that have not been previously reported in the context of CC, including glycerophosphodiester phosphodiesterase domain containing 3, interleukin 1 receptor type II, natriuretic peptide type C, MGAT4 family member C, lecithin-retinol acyltransferase (phosphatidylcholine-retinol-O-acyltransferase) and glucoside xylosyltransferase 2, was observed. Notably, upregulation of the serine (or cysteine) peptidase inhibitor clade B member 9 gene and downregulation of the Granzyme gene family were observed; the repression of the Granzyme B pathway may be a novel mechanism of immune evasion by cancer cells. The present results provide the basis for further studies on early biomarkers of CC risk and synergistic interactions between HR­HPV and oestrogen.

Utilization of blood spot testing for metabolic-genetic disorders in Honduras: is it time for newborn screening?

Honduran infant mortality (20/1000) has fallen below the Latin American newborn screening target rate (<30/1000). The authors report 2 Honduran maple syrup urine disease cases and a newborn screening pilot study. The first infant, diagnosed by plasma/urine testing in the U.S., prompted this study. Although marked clinical/radiological improvement occurred after treatment, moderate neurodevelopmental delays persist at 5 years. This 1-month, prospective study used blood spot specimens from hospitalized term Honduran neonates shipped overnight to South Carolina for routine newborn screening with electronic result submission to Honduras for follow-up. Of 88 consecutive neonates (mean age: 4.2 days, standard deviation: 4.2 days) tested, 24 (0.6%) of 3837 completed tests were positive. Another infant with maple syrup urine disease, diagnosed after study completion by blood spot testing, later died. The study findings indicate that collaborative blood spot testing aids in the diagnosis of Honduran metabolic-genetic disease. Newborn screening is now needed to diagnose and treat these diseases before morbidity/mortality develops.

Detección de inflamación en placa aterosclerosa: rol de la tomografía por emisión de positrones y de la proteína C reactiva / Detection of inflammation in an atherosclerose plaque: the role of the positron emission tomography and C reactive protein

OBJECTIVES: To demonstrate that inflammatory atheromatose carotid plaques can be visualized with positron emission tomography with 18F-fluorodeoxyglucose (18FDG PET) in symptomatic patients, in order to correlate them with systemic inflammatory markers, such as CRP. METHOD: Fifteen patients with cerebral ischemia due to atherosclerotic carotid disease were studied. 18FDG uptake with PET was considered and blood samples were taken for determining high sensibility C reactive protein (HsCRP). RESULTS: The mean age of the patients was 66 years; 11 of them were males (73%) and 4 were females (27%). 18FDG PET was positive in 12 patients (80%), while 100% of the studied population had low risk HsCRP with normal white cell count. CONCLUSIONS: 18FDG PET proves active inflammation in carotid atheromatose plaques. There was no significant correlation between the presence of ahteromatose carotid plaques, HsCRP serum levels, and 18FDG PET study.

[Detection of inflammation in an atherosclerose plaque: the role of the positron emission tomography and C reactive protein]. / Detección de inflamación en placa aterosclerosa: rol de la tomografía por emisión de positrones y de la proteína C reactiva.

OBJECTIVES: To demonstrate that inflammatory atheromatose carotid plaques can be visualized with positron emission tomography with 18F-fluorodeoxyglucose (18FDG PET) in symptomatic patients, in order to correlate them with systemic inflammatory markers, such as CRP. METHOD: Fifteen patients with cerebral ischemia due to atherosclerotic carotid disease were studied. 18FDG uptake with PET was considered and blood samples were taken for determining high sensibility C reactive protein (HsCRP). RESULTS: The mean age of the patients was 66 years; 11 of them were males (73%) and 4 were females (27%). 18FDG PET was positive in 12 patients (80%), while 100% of the studied population had low risk HsCRP with normal white cell count. CONCLUSIONS: 18FDG PET proves active inflammation in carotid atheromatose plaques. There was no significant correlation between the presence of ahteromatose carotid plaques, HsCRP serum levels, and 18FDG PET study.

Evaluación de la calidad de la atención a la salud mediante indicadores y su estándar / Evaluation of health care though indicators and standards

El objetivo del estudio es analizar críticamente los procesos de la atención a la salud, buscando la mejoría de los mismos con base en indicadores de calidad y a través de una estrategia participativa. Para su realización se conformó un grupo de diferentes categorías representativa de los servicios del hospital, el cual se capacitó y sensibilizó a través de una estrategia educativa de intervención; se analizó el proceso de atención, identificando objetivamente los problemas y proponiendo como mejorarlo a través de indicadores de calidad y su estándar. En general, el personal propuso algunos indicadores comunes; tratar en forma amable a los pacientes, puntualidad al inicio de labores; informar al derechohabiente, disminuir tiempos de espera, y procurar la satisfacción de los usuarios internos y externos. El estudio nos permite destacar a las estrategias participativas como elemento transformador de la cultura laboral, y señalar que se debe romper con los esquemas normativos rígidos, que convierten al trabajador en un receptor pasivo de normas y no le permiten el uso de su inteligencia y creatividad

Tornillo dinámico de cadera AO (DHS) en el tratamiento de las fracturas trocantéricas / AO Dynamic hip screw (DHS) for treatment of trochanteric fractures

El tratamiento de las fracturas trocantéricas ha representado siempre un problema para el cirujano ortopedista, por lo que a través del tiempo se han desarrollado diversos métodos de fijación y técnicas quirúrgicas para su solución. Se presentan 49 casos de fracturas trocantéreas tratadas quirúrgicamente mediante el tornillo dinámico de cadera AO (DHS), en el Servicio de Cirugía de Cadera y Pelvis del Hospital de Traumatología y Ortopedia ®Lomas Verdes¼ del IMSS, durante el periodo del 1o. de enero al 31 de diciembre de 1990, de uno u otro sexo, edad adulta, con diagnóstico de fractura trocantérica bifragmentada o multyfragmentada, a los cuales se les realizó evaluación clínica y radiográfica preoperatoria y postoperatoria inmediata, y a las 2, 4, 8 y 16 semanas. De los 49 pacientes, 29 eran hombres y 20 mujeres, con edad promedio de 68 años con fractura trocantérica multifragmentada en 22 casos y bifragmentada en 27; tiempo quirúrgico promedio de 55 minutos; sangrado transoperatorio promedio de 55 minutos; sangrado transoperatorio promedio de 300 cc, con consolidación radiográfica en el 100 por ciento, 2 complicaciones (una bursitis trocantérica y una protrusión cefálica del tornillo), evaluados por el método de Merle D'Aubigné; 46 casos excelentes, uno bueno, uno regular y uno malo. El tornillo dinámico de cadera AO en el tratamiento de las fracturas trocantéricas es en la actualidad el método de elección, ya que su técnica es sencilla, permite una rápida movilización y rehabilitación, con un bajo índice de complicaciones

Tratamieno de la cefalea de origen diverso con la combinación analgesica dihidroergotamina, butalbital, propitenazona y cafeína: estudio doble ciego contra placebo / Treatment of headaches of differnt origins with the analgesic combination dihydroergotamine, butalbital, propyphenazone and caffein: double-blind study against placebo

En un estudio doble ciego comparativo contra placebo, se incluyó a 37 pacientes con cefalea de origen diverso; 17 de ellos recibieron una combinación analgésica de mesilato de dehidroergotamina (0.5 mg), butalbital (45 mg), propifenazona (125 mg) y cafeína (40 mg) en dosis de dos grageas cada seis horas, hasta un máximo de seus grageas por día, quedando 20 pacientes que recibieron placebo, en presentación idéntica al medicamento estudiado. El origen de la cefalea fue diverso tanto en el grupo que recibió el principio activo como en el grupo placebo; la localización y evolución de las cefaleas fueron similares en ambos grupos. Mediante el tratamiento, que tuvo una duración de cinco días, la intensidad del dolor de acuerdo a una escala de valoración previamente establecida, descendió de 3.23 ñ 0.90 a 0.82 ñ 1.28 en el grupo tratado, mientras que en el grupo placebo el descenso no fue estadísticamente significativo. Se analizó también el número de grageas requeridas, tiempo de instalación del efecto terapéutico y su duración, así como los efectos indeseables que se presentaron en cada grupo. Se concluye que la combinación analgésica demostró ser útil en el tratamiento de la cefalea de diverso origen