Adolescent cybervictimization - Who they turn to and their perceived school climate.

The purpose of this study was to understand how adolescent cybervictims perceive their school climate and whether telling school community members, such as teachers, play a significant role in these perceptions. Another objective was to understand whether age and gender played a significant role in the relation between whom cybervictims told and their perceived school climate. The Cybervictims Scale for Adolescents and Children and the Perceived School Climate Scale were applied to 3525 Portuguese students of whom 218 were cybervictims attending 6th, 8th, and 11th grades. Results showed that even though adolescent cybervictims reported cybervictimization more to friends and parents, those who told teachers about their experience, tended to report more positive perceptions of their school climate. Gender and age did not play a significant role in the relationship between cybervictimization and perceived school climate. Implications of the findings are discussed with regards to the role of teachers and in-service training in preventing cyberbullying.

Genotoxic evaluation in Oreochromis niloticus (Fish: Characidae) of recombinant spore-crystal complexes Cry1Ia, Cry10Aa and Cry1Ba6 from Bacillus thuringiensis.

Bioinsecticides from Bacillus thuringiensis (Bt) are widely used around the world in biological control against larval stages of many insect species. Bt has been considered a biopesticide that is highly specific to different orders of insects, non-polluting and harmless to humans and other vertebrates, thus becoming a viable alternative for combating agricultural pests and insect vectors of diseases. The family of Bt δ-endotoxins are crystal-protein inclusions showing toxicity to insects' midgut, causing cell lysis leading to starvation, septicemia and death. The aim of this study is to evaluate the genotoxic potential of recombinant Bt spore-crystals expressing Cry1Ia, Cry10Aa and Cry1Ba6 on peripheral erythrocyte cells of Oreochromis niloticus, through comet assay, micronucleus (MN) test and nuclear abnormalities (NA) analysis. Fish (n = 10/group) were exposed for 96 h at 10(7) spores 30 l(-1), 10(8) spores 30 l(-1) or 10(9) spores 30 l(-1) of Bt spore-crystals. Cry1Ia showed a significant increase in comet cells at levels 1 and 2, but not at levels 3 and 4, so it was not mutagenic nor did it induce MN or NA. These three spore-crystals showed some fish toxicity at only the highest exposure level, which normally does not occur in the field.

Sexual Assault: Approach to Reality in the Area of Santiago de Compostela (Galicia, Spain) through a 12-Year Retrospective Study.

Sexual assault constitutes a severely traumatic experience that impacts the lives of far too many victims each year. The underlying behaviors of the offenders are often associated with psychological, physical and social distress, and the use of psychotropic substances was found in a good number of cases. A descriptive and retrospective review of sexual assault cases has been undertaken to identify trends in the toxicology findings in Drug-Facilitated Sexual Assault in Santiago de Compostela over the past 12 years. During this period, a total of 69 cases were referred to the Forensic Toxicology Service as sexual assault cases. The sex and age distribution of the cases showed that females between the ages of 14 and 65 years constituted the group most frequently submitted to sexual assault, with a peak of 55.1% in the 18- to 30-year age group. Alcohol consumption was positive in 77.1% of positive cases determined, followed by drugs (34.4%) and illicit drugs (26.2%). Our results showed a high percentage of alcohol consumption in sexual assault cases.

Disappearance of codeine, morphine and 6-MAM in hair after cessation of abuse.

Research on the determination of drugs of abuse in hair has established that drugs can be detected in hair even long after cessation of use. The purpose of this study was to analyze hair samples from chronic opioid users who were beginning a controlled drug cessation program. The study population (n = 15) is involved in a drug rehabilitation program in Santiago de Compostela, Spain. Over a 6-month period, subjects provided hair samples at 2-month intervals, with the first sample collected on the day they began the program. Codeine, morphine, and 6-MAM were analyzed by GC/MS (LOQ = 0.2 ng/mg). Hair tresses were divided into 1 cm segments and analyzed for all analytes 0-1 cm corresponding to the proximal portion to the scalp Following cessation of opioid use, traces of codeine, morphine, and 6-MAM still remained in the newly growing hair segments for a specified period. After 2 months, still 27 % of the users tested positive, and at 4 months, 20 % were positive but only for 6-MAM. However, after 6 months of abstinence, the results were negative for all analytes.

Detection of coca alkaloids in oral fluid from coca leaf (tea) consumers: using solid phase extraction to improve validation parameters and widen the detection window.

Hygrine and cuscohygrine, two coca leaf alkaloids, have been previously proposed as markers to differentiate legal and illegal cocaine consumption. This is a very common problem in some countries of South America, where the consumption of coca leaves has a long tradition. Analytical methods focusing on the assessment of coca leaf alkaloids, such as cuscohygrine, hygrine, tropacocaine and t-cinnamoylcocaine, in oral fluid are virtually non-existent in forensic toxicology laboratories worldwide due to their lack of application. However, the problem of differentiating legal and illegal cocaine use in criminal justice, DUID (drug-impaired driving) and WDT (workplace drug testing) programs is growing. Therefore, researchers are obliged to develop methods to measure coca leaf alkaloids (cuscohygrine, hygrine and t-cinnamoylcocaine) in biological matrices for further validation for routine analyses in forensic toxicology laboratories. This work aims to optimize a previously published separation method by protein precipitation in oral fluid by using solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) operating in multiple reaction monitoring (MRM) mode. The use of SPE allowed the matrix effect and the background to be reduced in the chromatograms due to the obtained cleaner extracts. Consequently, improved detection and quantification limits were reached. Findings showed that the detection windows for coca leaf alkaloids were longer than three hours in real oral fluid samples from volunteers who drank a cup of coca tea. These detection windows are quite higher than those previously obtained when using the method based on separation by protein precipitation.

Synergistic and threshold effects of GH1 and GHR promoter size variation on body growth and fat accrual in young Nelore (Bos indicus) bulls.

A synergistic effect in the somatotropic axis (GH1-GHR-IGF1) was observed in 736 young Nelore (Bos indicus) bulls under ad libitum grass feeding conditions on irrigated pasture in central Brazil. Stepwise substitution of shorter alleles of the promoter region of the growth hormone gene (GH1) and the P1 promoter of the GH1 receptor gene (GHR) with longer alleles was associated with significantly increased body weight gain (W550, weight at age 550 days; ADG, average daily gain) and fat accrual (FAT, rib eye fat thickness). A threshold effect on ADG was associated with allele size variation at the GH1. A best fit model indicated a 3- to 6-fold effect of GH1 variation on ADG, when compared to the variation at the GHR and a known microsatellite at the somatomedin gene (IGF1, insulin-like growth factor 1). A threshold effect on FAT was associated with substitution of the short GHR allele by the longer GHR alleles; the effect of the GHR variation on FAT was 10-fold that of the variation at the GH1 and IGF1 loci. Among the 10 GH1-GHR-IGF1 multi-genotypes identified, the predominant genotype was homozygous for the large GH1 promoter (long/long, G2/G2 or domestic type), short GHR promoter (short/short or wild type), and short IGF1 microsatellite (short/short or wild type). This predominant multi-genotype suggests that selection pressure in the Nelore breed has been directed towards high ADG and W550, and low FAT. Our results mirror previous findings in the oMtla-oGH transgenic mouse model, in which the level of somatotropic gene expression acts through a threshold mechanism, and low expression results in adipogenesis, while high expression increases body growth.

Determination of Seven Antidepressants in Pericardial Fluid by Means of Dispersive Liquid-Liquid Microextraction (DLLME) and Gas Chromatography-Mass Spectrometry (GC/MS).

Although blood is often used to detect and quantify the presence of drugs, there are some instances where samples obtained from other biological matrices, like pericardial fluid (PF), are necessary since adequate blood samples may not be available. PF is an epicardial transudate, which contains plasma components that include toxicological substances making this sample useful when blood samples are not available. This fluid is a well preserved postmortem sample and can easily be collected in larger amounts without significant contamination, compared with other body fluids. Although studies involving PF began around the 1980's, the adequacy of such fluid as a biological matrix has been poorly investigated. Antidepressants are frequently detected in postmortem samples from forensic cases. Nowadays, they constitute some of the most commonly prescribed drugs worldwide. A total of seven antidepressants (venlafaxine, mirtazapine, olanzapine, paroxetine, sertraline, fluoxetine and citalopram) were evaluated in this study. A new extraction method involving dispersive liquid-liquid microextraction (DLLME) is presented in which chloroform and acetonitrile are determined to be the best extraction and dispersing solvents. The experimental design was achieved using StatGraphics 18. The Response Surface Methodology enabled us to know the optimal volume for the two solvents used in the DLLME. The detection technique used was gas chromatography-mass spectrometry (GC-MS) with electron impact ionization as ionization source. A temperature gradient has been used and the total chromatographic separation time was 19.43 min. Validation results met the international validation guidances (FDA). Under the optimal condition, the method offered good validation parameters showing a new efficient, simple, rapid, and sensitive method. The analytical method was applied to thirty-one pericardial fluid samples. Twenty-one samples were positive with concentrations between 0.19 and 8.48 µg/mL. Venlafaxine and olanzapine were the antidepressants most frequently found.

Survival of the thriftiest: restricted nurture reveals the thrifty nature of a growth gene in Bos indicus.

Growth hormone (GH) is a part of the somatotropic axis that controls metabolism, growth, development and aging in a wide range of animals. Mutations that reduce GH signaling have been associated with extended life spans and increased longevity in ways similar to what is observed in dietary restriction (DR) models. However, the mechanism by which DR works is not well understood. Here, we show that DR works as a factor in the evolution of the genetic make-up of domestic cattle. In a series of 6864 bovines of seven Bos indicus and tropically adapted Bos taurus breeds, the frequency of a short, wild-type allele of the promoter region of the bovine GH gene, G1 allele, varied from 2.7 to 17.7%. The frequency of the long, domestic G2 allele increased from 88 to 95% along 20 calf crops of commercial Bos indicus cattle of the Nelore breed undergoing selection for increasing post-weaning weight gain with ad libitum nutrient intake. Under DR, however, the G1 allele sustained growth better than the G2 allele, as observed in a series of feeding tests. The G2 allele was even detrimental or abiotropic, as it caused rapid body decay under DR. We observed a reflection symmetry of GH allele substitution effects on body weight under different dietary schemes. The G2 allele is featured as the "demanding allele", because it is optimally fitted to ad libitum nutrient intake. The G1 allele is featured as the "thrifty allele" because it is optimally fitted to DR. Our results show that dietary regimens need not extend lifespan or increase longevity in the sense of age-specific fitness. Instead, adaptation to any particular dietary regimen is just as much a consequence of selection as its cause; dietary regimens work as do any selection force, optimizing genotypic fitness to nutritional conditions.

Determination of benzodiazepines in pericardial fluid by gas chromatography-mass spectrometry.

In Forensic Toxicology it is sometimes impossible to obtain a valid blood sample to perform toxicological analysis due to several factors like advanced state of decomposition, severe burns, bleed to death…. Pericardial Fluid has already been studied during the last years and has been proposed as a valid specimen for toxicological tests. Over the years, the consumption of benzodiazepines spread among the drug dependent population and became noticeable in drug facilitated assault cases and road accidents. Improvement of the analytical methodology required for detecting the presence of these drugs in biological samples is of great importance for forensic toxicology, in order to correctly diagnose an exposure or a poisoning. In this study, 9 benzodiazepines (diazepam, nordiazepam, midazolam, bromazepam, oxazepam, temazepam, lorazepam, clonazepam and alprazolam) have been determined in pericardial fluid. For this purpose a solid phase extraction (SPE) was carried out using Bond Elut Certify cartridges. After the derivatization of six of the nine benzodiazepines, gas chromatography coupled to a selective mass detector was used as the technique for the separation of the analytes. The method developed was fully validated for the 9 analytes and was applied to real samples of pericardial fluid received at the Forensic Toxicology Service of the University of Santiago de Compostela. Finally, they were compared with blood results looking for the existence of a possible correlation between both biological samples.

Anticaries effect of low-fluoride dentifrices with phosphates in children: A randomized, controlled trial.

UNLABELLED: Low-fluoride dentifrices (LFD) have been recommended for young children aiming to minimize excessive fluoride intake during tooth brushing. Given the uncertainties surrounding the clinical efficacy of such formulations, alternatives to increase their anticaries effect have been investigated. OBJECTIVES: This double-blind, randomized controlled trial assessed the clinical efficacy of LFDs supplemented with Calcium Glycerophosphate (CaGP) or Sodium Trimetaphosphate (TMP) on the progression of dental caries in the deciduous dentition. METHODS: Children (average age 48 months old) from two Brazilian cities (Araçatuba and Fernandópolis) were randomly assigned into 3 groups, according to the dentifrice to be used: 500ppm F plus 1% TMP ("500TMP", n=206), 500ppm F plus 0.25% CaGP ("500CaGP, n=201) and 1100ppm F ('1100F', n=193). Clinical exams (dmfs) were performed at baseline and 18 months after dentifrices started to be used, and the increment in the number of carious lesions (final dmfs - initial dmfs) was calculated. Data were analyzed by multivariate linear regression analysis to verify the influence of city, gender, previous caries experience and type of dentifrice on dmfs increment (p<0.05). RESULTS: Mean caries increment observed for 500TMP (0.26) was significantly lower when compared with 1100F (0.74), while values found for 500CaGP (0.54) were not significantly different from 1100F. Caries increment was significantly higher in children from Araçatuba and in those with previous caries experience. CONCLUSION: The results indicate that clinical efficacy of LFDs supplemented with TMP is superior to that observed for a conventional formulation (1100F), while the addition of CaGP leads to similar efficacy when compared to 1100F. CLINICAL SIGNIFICANCE: Children brushing with 500ppm F toothpastes containing phosphate salts developed fewer caries lesions when compared with those using a 1100ppm F dentifrice. The tested toothpastes can be regarded as a safe alternative to conventional formulations for children under 6 years of age, based on risk-benefit considerations.

Identification of three novel mutations in hereditary protein S deficiency.

We report the application of single-stranded conformation polymorphism (SSCP) analysis to the screening of 15 functionally important Protein S (PS) gene (PS alpha) regions (4.243 Kb) in 6 unrelated families with PS deficiencies. Direct sequencing of the fragments with altered migration patterns led to the identification of the corresponding molecular alterations. A missense mutation, G to T transversion at codon Cys598, and two different alterations, leading either to allelic exclusion, or premature termination of the protein translation: a G to A transition at codon Trp465 and a 1 nt (T) insertion at codon 265, were identified. The 1 nt insertion was observed in three apparently unrelated families but with a common geographical origin and the mutated allele was undetectable in platelet mRNAs of affected individuals. Family analysis confirmed, in each case, a perfect cosegregation of the mutation with the PS deficiency. We conclude that these alterations represent the causative mutations.

Evaluation of 2 intravenous thrombolytic agents (anisoylated plasminogen streptokinase activator complex versus streptokinase) in patients with acute myocardial infarction.

Ten patients with symptoms of acute myocardial infarction of less than 6 hours duration were randomised to receive either anisoylated plasminogen streptokinase activator complex [APSAC] (30U) or streptokinase (1,500,000U) intravenously. The aims of the study were to compare the angiographic patency of the infarct-related coronary arteries and to monitor drug safety and tolerance for up to 24 hours. The left anterior descending artery was occluded in 3, the left circumflex in 3 and right coronary artery in 4 patients. Time between onset of pain and treatment ranged from 150 to 330 minutes. At 90 minutes, 8 patients, 3 of 5 (60%) of the APSAC group and all of the streptokinase group, had patent arteries. No significant differences were found in measurements of coagulation. There were no haemorrhagic complications. One patient of the APSAC group had reinfarction 6 hours after treatment and died in cardiogenic shock. APSAC seems safe and is easier to use than streptokinase, and both agents result in patency in the majority of patients, although too few patients were included to allow a valid comparison. However, thrombolysis should be considered only a temporary solution in acute myocardial infarction, associated mainly with 3-vessel disease.

[Prevention of thrombogenesis in the extracorporeal circuit of hemodialysis with a low molecular heparin: standardization of the dosage with a better hemorrhagic risk/effectiveness ratio]. / Prevenção da trombogénese no circuito extracorporal de hemodiálise com uma heparina de baixo peso molecular: padronização da dose com melhor relação risco hemorrágico/eficácia operacional.

PURPOSE: To test the efficacy and safety of a low molecular. Weight heparin (LMWH)--Fraxiparine, for hemodialysis (HD) anticoagulation, compared with conventional heparin (H) or serum lavage without other anticoagulation (L). DESIGN: Prospective controlled study. PATIENTS AND METHODS: Twenty-nine consecutive patients referred for dialysis in a tertiary care hospital were divided in 3 groups A, B and C, each group A and B patient submitted to 2 dialysis, AI and AII, BI and BII. Group A--n = 10, no bleeding risk, single needle technique, blood flow (Qb) less than 200 ml/min. HD-AI used LMWH 10,000 U pre-HD, HD-AII used H for an ACT 1.5 to 2 times baseline; group B--n = 10, high bleeding risk, double needle dialysis, Qb--200 to 300 ml/min. HD-BI used LMWH 5000 U pre-HD, and HD-BII used only L; Group C--n = 9, no bleeding risk, Qb less than 200 ml/min, all received LMWH 5000 U pre-HD. A semiquantitative screening was done in each dialysis for the presence of dialyser or venous chamber clots, APTT and Anti Xa activity were measured every 30 min., as well as pre and post-dialysis Hb, Htc, and platelets. RESULTS: APTT didn't rise significantly during HD with LMWH in contrast with the AII group with H (32.2 +/- 7.1 vs 63 +/- 25.8, p less than 0.05). The APTT levels in all dialysis with LMWH were identical to BII dialysis With L. Anti xa activity had an early peak at 30 to 60 min. With LMWH (0.62 +/- 0.45 em AI) and a late one at 180 min with H (0.39 +/- 0.2). There was no significant differences between pre and post-dialysis corrected platelet counts, but the lavage group showed the greater decrements (-20% +/- 24). In all the 49 dialysis we had 5 cases of complete clotting of the blood circuit, all of them in the lavage group C. No patients with high risk of hemorrhage had any bleeding increment. CONCLUSION: LMWH prevents clotting as effectively as H, in low doses of 5000 anti Xa units it doesn't interfere with PTT and is far more effective than HD with serum lavage in patients with bleeding risk and/or low blood flow in the dialysis circuit.

[Possible participation of the antidiuretic hormone in the inhibiting action of at on gastric secretion]. / O vozmozhnom uchastii antidiureticheskogo gormona v tormoziashchem deistvii zhira na zheludochnuiu sekretsiiu.

The experiments were performed on dogs with isolated pouches (according to Pavlov, Heidenhain and Gregory) to study the action of antidiuretic hormone (ADH) on gastric secretion produced by a food irritant (100 g of meat) and by administration of histamine and pentagastrin. ADH was shown to exert an inhibitory action on gastric secretion induced by food or humoral irritants in dogs with isolated pouches according to Pavlov and Heidenhain. In dogs with completely denervated isolated pouches, food irritant-induced gastric secretion was suppressed for 2 1/2--3 1/2 h. Then it exceeded the control level. During ADH administration the total acidity and the content of free hydrochloric acid noticeably decreased as compared to control. There was also a clear-cut tendency to a reduction in the concentration of common proteinases in gastric juice. Adrenoblockers abolished the inhibitor action of ADH on gastric secretion produced by food or humoral irritants, while the inhibitory action of fat was not reversed by phentolamine or obsidan. The data obtained indicate a different mechanism of the inhibitory effect of fat and ADH on gastric secretion.

[Effect of fats on gastric secretion in a varying degree of innervation of the isolated stomach]. / Vliianie nekotorykh zhirov na zheludochnuiu sekretsiiu pri razlichnoi stepeni innervatsii izolirovannogo zheludka.

On the ground of an investigation on dogs with different types of isolated stomachs a characteristics of peculiarities of the action on the gastric secretion by three dissimilar fats is given, viz. butter, sunflower and corn oils. The investigated fats differ considerably by the lengthy inhibition of the gastric secretion produced by meat, and to a still greater degree by the intensity of the 2nd phase of secretion (after inhibition). It is also shown that with a complete extramural denervation of the isolated stomach (after Gregory) the inhibitory action of fats remains to be strongly marked. However, in this case after the period of inhibition, in the 2nd phase a significantly reduced secretion of the gastric juice is observed.

[Mechanism of the inhibitory effect of fat on gastric secretion]. / K mekhanizmu tormoziashchego deistviia zhira na zheludochnuiu sekretsiiu.

Experiments on dogs were made to demonstrate the importance of humoral factor for the inhibitory action of fat. The mechanism of the effect of fat and antidiuretic hormone on gastric secretion was found to be different. Fatty emulsion was discovered to produce an inhibitory action on gastric secretion when administered parenterally, while lipid secretion with bile to the duodenum to be of importance. The inhibitory effect of prostaglandin E2 on gastric juice secretion was studied. It has been demonstrated that this action is not removed by adrenoblockers.

Atividade antibacteriana de Óleos Essenciais sobre Streptococcus mutans e Staphylococcus aureus / Antibacterial Activity of Essential Oils against Strains of Streptococcus and Staphylococcus

Este trabalho objetivou avaliar a ação antimicrobiana in vitro dos óleos essenciais de Ocimum basilicum (Manjericão Exótico), Thymus vulgaris (Tomilho Branco), e de Cinnamomum cassia (Canela da China) sobre cepas bacterianas de Streptococcus mutans (ATCC 25175) e Staphylococcus aureus (ATCC 25923). A atividade antibacteriana dos óleos essenciais foi determinada pela Concentração Inibitória Mínima (CIM) e a Concentração Bactericida Mínima (CBM) através da técnica de microdiluição e do esgotamento. Para a CIM, foram utilizadas placas de 96 poços e inseriu-se 100µL de caldo BHI, 100µL da diluição dos óleos essenciais no primeiro poço e 10µL da suspensão bacteriana (1,5x10(6) microrganismos/mL). Realizou-se a diluição seriada partindo-se da concentração inicial de 8% até 0,0625%. A CIM correspondeu à última diluição na qual não foi verificada a presença de bactérias. Para obter a CBM, realizou-se a semeadura em Ágar Miller-Hinton das diluições correspondentes a CIM, 2CIM e 4CIM. As placas foram incubadas a 37º C em estufa bacteriológica por 24 horas. Os testes foram realizados em triplicata tendo a clorexidina como controle positivo. Para S. aureus (ATCC 25923) a CIM e CBM dos óleos essenciais de C. cassia, O. basilicum e T. vulgaris foram 0,0625%, 4% e 0,0625%, respectivamente. Para S. mutans a CIM e a CBM dos óleos essenciais de C. cassia e T. vulgaris foram 0,125% e 0,25%, respectivamente. Já a CIM do O. basilicum foi 4% e não apresentou ação bactericida. Conclui-se que os óleos essenciais avaliados apresentaram ação antibacteriana frente a cepas de S. mutans e S. aureus, sendo que os menores valores de CIM e de CBM foram provenientes dos óleos de C. cassia e T. vulgaris.

The aim of this study is to evaluate the in vitro antimicrobial activity of essential oils of Ocimum basilicum (basil), Thymus vulgaris (thyme) and Cinnamomum cassia (Chinese cinnamon) against strains of Streptococcus mutans (ATCC 25175) and Staphylococcus aureus (ATCC 25923). The antibacterial activity of the essential oils was determined by Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). The MIC was obtained by the microdilution technique using 96-well microplates, in which we inserted: 100µL of Brain Heart Infusion broth at double concentration, 100µL of the dilution of the essential oils and 10µL of bacterial suspension (1.5 x 10(6) organisms / mL). The products were diluted from the initial concentration of 8% up to 0.0625%. The MIC corresponded to the last dilution in which there was no presence of bacteria or turbidity in the culture medium. The MBC was obtained by seeding, in Mueller-Hinton agar, 10µL aliquots of dilutions corresponding to the MIC and the two immediately preceding ones (2MIC and 4MIC). The plates were incubated at 37°C in a bacteriological incubator for 24 hours. The tests were performed in triplicate, and 2% Chlorhexidine Digluconate was the control product. For S. aureus, the MIC and MBC of the essential oils of C. cassia, O. basilicum and T. vulgaris were 0.0625%, 0.0625% and 4%, respectively. For S. mutans, the MIC and MBC of the essential oils of C. cassia and T. vulgaris were 0.125% and 0.25%, respectively. The MIC of O. basilicum against S. mutans was 4% and the essential oil showed no bactericidal action. Chlorhexidine Digluconate presented antibacterial activity against all organisms. The evaluated essential oils presented antibacterial activity against the strains of S. mutans and S. aureus, and we highlight the essential oils from C. cassia and T. vulgaris with the lowest MIC and MBC.