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Abstract Metabolic reprogramming (MR) influences progression of chronic myeloid leukaemia (CML) to blast crisis (BC), but metabolic programs may change transiently in a second dimension (metabolic plasticity, MP), driven by environments as hypoxia, affecting cytotoxic potency (CPot) of drugs targeting mitochondria or mitochondria-related cell stress responses (MRCSR) such as mitophagy and mitochondrial biogenesis. We assessed mitochondrial membrane potential (MMP), mitochondrial mass (MM), apoptosis, glucose uptake (GU), and CPot of arsenic trioxide (ATO), CCCP, valproic acid (VPA), vincristine (VCR), Mdivi1, and dichloroacetic acid (DCA) in CML BC cells K562 (BC-K562) under hypoxia through flow cytometry, and gene expression from GEO database. About 60% of untreated cells were killed after 72 h under hypoxia, but paradoxically, all drugs but ATO rescued cells and increased survival rates to almost 90%. Blocking mitophagy either with VCR or Mdivi1, or increasing mitochondrial biogenesis with VPA enhanced cell-survival with increased MM. DCA increased MM and rescued cells in spite of its role in activating pyruvate dehydrogenase and Krebs cycle. Cells rescued by DCA, VPA and CCCP showed decreased GU. ATO showed equal CPot in hypoxia and normoxia. MP was evidenced by differential expression of genes (DEG) under hypoxia related to Krebs cycle, lipid synthesis, cholesterol homeostasis, mitophagy, and mitochondrial biogenesis (GSE144527). A 25-gene MP-signature of BC-K562 cells under hypoxia identified BC cases among 113 transcriptomes from CML patients (GSE4170). We concluded that hypoxic environment drove a MP change evidenced by DEG that was reflected in a paradoxical pro-survival, instead of cytotoxic, effect of drugs targeting mitochondria and MRCSR.

Abstract Background To describe the effect of mechanical ventilation on diaphragm mitochondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis. Methods A cecal ligation and puncture (CLP) protocol was performed in 12 rats while 12 controls underwent sham operation. Half of the rats in each group were paralyzed and mechanically ventilated. We performed blood gas analysis and lactic acid assays 6 h after surgery. Afterwards, we measured diaphragm strength and mitochondrial oxygen consumption, ATP and ROS generation, and cytochrome c oxidase activity. We also measured malondialdehyde (MDA) content as an index of lipid peroxidation, and mRNA expression of the proinflammatory interleukin-1β (IL-1β) in diaphragms. Results CLP rats showed severe hypotension, metabolic acidosis, and upregulation of diaphragm IL-1β mRNA expression. Compared to sham controls, spontaneously breathing CLP rats showed lower diaphragm force and increased susceptibility to fatigue, along with depressed mitochondrial oxygen consumption and ATP production and cytochrome c oxidase activity. These rats also showed increased mitochondrial ROS generation and MDA content. Mechanical ventilation markedly restored mitochondrial oxygen consumption and ATP production in CLP rats; lowered mitochondrial ROS production by the complex 3; and preserved cytochrome c oxidase activity. Conclusion In an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function.

INTRODUCTION:Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous "pouches." Some snus products undergo tobacco pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers. METHODS:Moisture, pH, nicotine, and tobacco-specific N'-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured. RESULTS:Among all product types, moisture (27.4%-59.5%), pH (pH 5.87-9.10), total nicotine (6.81-20.6 mg/g, wet), unprotonated nicotine (0.083-15.7 mg/g), and total TSNAs (390-4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol. CONCLUSION:Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered "equivalent". Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.

Cumulative receiver operator characteristic (ROC) curve analysis extends classic ROC curve analysis to discriminate three or more ordinal outcome levels on a shared continuous scale. The procedure combines cumulative logit regression with a cumulative extension to the ROC curve and performs as expected with ternary (three-level) ordinal outcomes under a variety of simulated conditions (unbalanced data, proportional and non-proportional odds, areas under the ROC curve [AUCs] from 0.70 to 0.95). Simulations also compared several criteria for selecting cutpoints to discriminate outcome levels: the Youden Index, Matthews Correlation Coefficient, Total Accuracy, and Markedness. Total Accuracy demonstrated the least absolute percent-bias. Cutpoints computed from maximum likelihood regression parameters demonstrated bias that was often negligible. The procedure was also applied to publicly available data related to computer imaging and biomarker exposure science, yielding good to excellent AUCs, as well as cutpoints with sensitivities and specificities of commensurate quality. Implementation of cumulative ROC curve analysis and extension to more than three outcome levels are straightforward. The author's programs for ternary ordinal outcomes are publicly available.

The quality of power and current control are the greatest challenges of grid-connected wind farms during abnormal conditions. The negative- and positive-sequence components of the grid currents may be injected into a wind generation system during grid faults, which can affect the power stability and damage the wind system. The proposed work assures a low-voltage ride through capability of doubly-fed induction generator- based wind turbines under the grid voltage sag. A new technique to protect the wind system and to recompense the reactive power during failures of the utility grid according to the Spanish grid code is proposed. The control design is implemented to the power converters, and the grid current regulation is developed by using proportional-resonant regulators in a stationary two-phase (αβ) reference frame. The control performance is significantly validated by applying the real-time simulation for the rotor-side converter and the hardware in the loop simulation technique for the experiment of the generator’s grid-side converter control.

This article deals with the vector control in dq axes of a three-phase grid-connected photovoltaic system with single-stage topology and low-voltage-ride-through capability. The photovoltaic generator is built using an array of several series-parallel Suntech PV modules and is modeled as a Lookup Table (two-dimensional; 2-D). The requirements adopted when grid voltage sags occur are based in both the IEC 61400-21 European normative and the allowed amount of reactive power to be delivered according to the Spanish grid code, which avoids the disconnection of the inverter under grid faults by a limitation in the magnitude of the three-phase output inverter currents. For this, the calculation of the positive- and negative-sequences of the grid voltages is made and a conventional three-phase Phase-Locked Loop is used for the inverter-grid synchronization, allowing the control of the active and reactive powers solely with the dq components of the inverter currents. A detailed enhanced flowchart of the control algorithm with low-voltage-ride-through capability is presented and several simulations and experiments using Matlab/SIMULINK and the Controller Hardware-in-the-Loop simulation technique, respectively, are run for several types of one- and three-phase voltage sags in order to validate its behavior.

This review article is mainly oriented to the control and applications of modular multilevel converters (MMC). The main topologies of the switching modules are presented, for normal operation and for the elimination of DC faults. Methods to keep the capacitor voltage balanced are included. The voltage and current modulators, that are the most internal loops of control, are detailed. Voltage control and current control schemes are included which regulate DC link voltage and reactive power. The cases of unbalanced and distorted networks are analyzed, and schemes are proposed so that MMC contribute to improve the quality of the grid in these situations. The main applications in high voltage direct current (HVDC) transmission along with other medium voltage (MV) and low voltage (LV) applications are included. Finally, the application to offshore wind farms is specifically analyzed.

BACKGROUND: Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment) and acrolein's comparatively potent inhalation reference concentration of 0.02 µg/m3. OBJECTIVES: Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. METHODS: NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old) in the NHIS (National Health Interview Survey) 2000-2009 (n = 271,348 subjects). A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. RESULTS: In the highest quintile of outdoor acrolein exposure (0.05-0.46 µg/m3), there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI] = 1.08 [0.98∶1.19]) relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29]) in a model limited to never smokers (n = 153,820). CONCLUSIONS: Chronic exposure to outdoor acrolein of 0.05-0.46 µg/m3 appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population.

BACKGROUND: Arsenic is an ubiquitous element linked to carcinogenicity, neurotoxicity, as well as adverse respiratory, gastrointestinal, hepatic, and dermal health effects. OBJECTIVE: Identify dietary sources of speciated arsenic: monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). METHODS: Age-stratified, sample-weighted regression of NHANES (National Health and Nutrition Examination Survey) 2003-2010 data (∼8,300 participants ≥6 years old) characterized the association between urinary arsenic species and the additional mass consumed of USDA-standardized food groups (24-hour dietary recall data), controlling for potential confounders. RESULTS: For all arsenic species, the rank-order of age strata for median urinary molar concentration was children 6-11 years > adults 20-84 years > adolescents 12-19 years, and for all age strata, the rank-order was DMA > MMA. Median urinary molar concentrations of methylated arsenic species ranged from 0.56 to 3.52 µmol/mol creatinine. Statistically significant increases in urinary arsenic species were associated with increased consumption of: fish (DMA); fruits (DMA, MMA); grain products (DMA, MMA); legumes, nuts, seeds (DMA); meat, poultry (DMA); rice (DMA, MMA); rice cakes/crackers (DMA, MMA); and sugars, sweets, beverages (MMA). And, for adults, rice beverage/milk (DMA, MMA). In addition, based on US (United States) median and 90th percentile consumption rates of each food group, exposure from the following food groups was highlighted: fish; fruits; grain products; legumes, nuts, seeds; meat, poultry; and sugars, sweets, beverages. CONCLUSIONS: In a nationally representative sample of the US civilian, noninstitutionalized population, fish (adults), rice (children), and rice cakes/crackers (adolescents) had the largest associations with urinary DMA. For MMA, rice beverage/milk (adults) and rice cakes/crackers (children, adolescents) had the largest associations.

Industrial activities are increasingly dependent on each other. Several recent events (e.g. Tsunami and earthquake in Japan in 2011) illustrate the consequences (e.g. humans, economic…) of interactions between industrial infrastructures. The state-of-the-art review focused mainly on the risk assessment and interdependencies between critical infrastructures. The aim of this paper is to present an approach able to determine an infrastructure vulnerability level and risk scenarios development based on Seveso regulations and critical infrastructures. The vulnerability infrastructure level is assessed with a multi-criteria analysis. The goal is to identify several criteria according to physic, functional, economic, social and environment context of the infrastructure in the territory. The risk scenarios are developed in order to estimate the consequences in a territory of a threat on one or several infrastructures.

Background: Heterocyclic aromatic amines (HAA) are a group of hazardous substances produced during combustion of tobacco or high-temperature cooking of meats. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is a major carcinogenic HAA in tobacco smoke. Methods: Urinary AαC, used as a marker of AαC exposure, was analyzed on spot urine samples from adult participants of the 2013-2014 cycle of the National Health and Nutrition Examination Survey (N = 1,792). AαC was measured using isotope-dilution liquid chromatography-tandem mass spectrometry. Exclusive combusted tobacco smokers were differentiated from nonusers of tobacco products through both self-report and serum cotinine data. Results: Among exclusive smokers, sample-weighted median urinary AαC was 40 times higher than nonusers. Sample-weighted regression models showed that urinary AαC increased significantly with serum cotinine among both exclusive tobacco users and nonusers with secondhand smoke exposure. Among nonusers, eating beef cooked at high temperature was associated with a significant increase in urinary AαC, whereas consuming vegetables was associated with decreased AαC. In addition, smoking one-half pack of cigarettes per day was associated with a significant increase of 23.6 pg AαC/mL calculated at geometric mean of AαC, controlling for potential confounders. In comparison, increase in AαC attributable to consuming the 99th percentile of beef cooked at high temperature was 0.99 pg AαC/mL. Conclusions: Both exclusive smokers and nonusers of tobacco in the general U.S. population are exposed to AαC from tobacco smoke, with additional, lesser contributions from certain dietary components. [ABSTRACT FROM AUTHOR]

Introducción: internacionalmente resulta de interés mejorar la calidad de vida de hombres y mujeres, por ello es importante la detección temprana de problemas de salud como aquellos relacionados con la sexualidad. Objetivo: describir los aspectos principales relacionados con el inicio de relaciones coitales en adolescentes. Métodos: investigación observacional, descriptiva, transversal. El universo lo constituyeron los alumnos y alumnas de tres escuelas de enseñanza preuniversitaria; la muestra estuvo representada por 450 estudiantes seleccionados de forma estratificada e intencional, 150 jóvenes por centro; 50 de cada año académico comprendido entre los 15 y 18 años de edad. Se aplicó una encuesta validada por el Ministerio de Educación en el 2005. Resultados: se constató que en los muchachos las relaciones coitales se iniciaron más frecuentemente a los 14 años, cuando cursaban la secundaria básica; y a los 15 años en las muchachas, en el preuniversitario. El empleo de preservativo en la primera relación coital, los chicos lo refirieron en el 55,2 % de los casos y las chicas solo constituyeron el 49,8 %. Como lugares para su primera relación coital refirieron la casa de uno de los miembros de la pareja y las escuelas becadas. La novia o el novio fueron por lo general las personas con quienes se iniciaron sexualmente. Los adolescentes buscan con mayor frecuencia la satisfacción sexual, la compañía y la confianza; mientras que las adolescentes buscan apoyo, afecto, comprensión y confianza. Conclusiones: se evidenció la persistencia de patrones socialmente heredados relacionados con estereotipos de género, poca percepción de riesgo de contraer infecciones de transmisión sexual y tendencia a inicio de relaciones coitales en etapas tempranas de la adolescencia, sobre todo en los muchachos.