In vitro evaluation of the selective cytotoxicity and genotoxicity of three synthetic ortho-nitrobenzyl derivatives in human cancer cell lines, with and without metabolic activation.

Although the presence of nitro groups in chemicals can be recognized as structural alerts for mutagenicity and carcinogenicity, nitroaromatic compounds have attracted considerable interest as a class of agents that can serve as source of potential new anticancer agents. In the present study, the in vitro cytotoxicity, genotoxicity, and mutagenicity of three synthetic ortho-nitrobenzyl derivatives (named ON-1, ON-2 and ON-3) were evaluated by employing human breast and ovarian cancer cell lines. A series of biological assays was carried out with and without metabolic activation. Complementarily, computational predictions of the pharmacokinetic properties and druglikeness of the compounds were performed in the Swiss ADME platform. The MTT assay showed that the compounds selectively affected selectively the cell viability of cancer cells in comparison with a nontumoral cell line. Additionally, the metabolic activation enhanced cytotoxicity, and the compounds affected cell survival, as demonstrated by the clonogenic assay. The comet assay, the cytokinesis-block micronucleus assay, and the immunofluorescence of the γ-H2AX foci formation assay have that the compounds caused chromosomal damage to the cancer cells, with and without metabolic activation. The results obtained in the present study showed that the compounds assessed were genotoxic and mutagenic, inducing double-strand breaks in the DNA structure. The high selectivity indices observed for the compounds ON-2 and ON-3, especially after metabolic activation with the S9 fraction, must be highlighted. These experimental biological results, as well as the theoretical properties predicted for the compounds have shown that they are promising anticancer candidates to be exploited in additional studies.

Perturbation-based balance training leads to improved reactive postural responses in individuals with Parkinson's disease and freezing of gait.

Perturbation-based balance training (PBT) exposes individuals to a series of sudden upright balance perturbations to improve their reactive postural responses. In this study, we aimed to evaluate the effect of a short PBT program on body balance recovery following a perturbation in individuals with freezing of gait due to Parkinson's disease. Volunteers (mean age = 64 years, SD = 10.6) were pseudorandomly assigned either to a PBT (n = 9) or to a resistance training (RT, n = 10) group. PBT was implemented through balance perturbations varying in the kind, direction, side and magnitude of support base displacements. Both groups exercised with progressive difficulty/load activities twice a week for 4 weeks. Specific gains and generalization to dual-tasking and faster-than-trained support base displacements were evaluated 24 h after the end of the training, and retention was evaluated after 30 days of no training. Results showed that, compared with RT, PBT led to more stable postural responses in the 30-day retention evaluation, as indicated by decreased CoP displacement, velocity and time to direction reversal and reduced numbers of near-falls. We found no transfer either to a dual task or to a higher perturbation velocity. In conclusion, a training program based on diverse unpredictable balance perturbations improved the stability of reactive postural responses to those perturbations suffered during the training, without generalization to more challenging tasks.

Evaluation of oxidative damage to biomolecules and inflammation in patients with urea cycle disorders.

Urea cycle disorders (UCD) are inborn errors of metabolism that occur due to a loss of function in enzymes and transporters involved in the urea cycle, causing an intoxication by hyperammonemia and accumulation of metabolites. Patients can develop hepatic encephalopathy (HE), severe neurological and motor disabilities, and often death. The mechanisms involved in the pathophysiology of UCD are many and complex, but there are strong indications that oxidative stress and inflammation are present, being responsible for at least part of the cellular damage that occurs in these diseases. The aim of this study was to evaluate oxidative and nitrosative damage and inflammation in UCD, to better understand the pathophysiology mechanisms of these diseases. We evaluated the nitrite and nitrate content, thiobarbituric acid-reactive substances (TBARS), carbonyl protein content and a panel of cytokines in plasma sample of 14 patients. The UCD patients group consisted of individuals affected with ornithine transcarbamylase deficiency (n = 8), carbamoyl phosphate synthetase deficiency (n = 2), argininosuccinate synthetase deficiency (n = 2); arginase 1 deficiency (n = 1) and argininosuccinate lyase deficiency (n = 1). Patients mean age at diagnosis was 5.25 ± 9.86 years-old and mean concentrations were compared with healthy individuals of matched age and gender. We found a significant reduction in nitrogen reactive species in patients when compared to controls. TBARS was increased in patients, indicating lipid peroxidation. To evaluate protein oxidative damage in UCD, the carbonyl content was measured, and the results also demonstrated an increase in this biomarker. Finally, we found that UCD patients have enhanced concentrations of cytokines, with pro-inflammatory interleukins IL-6, IL-8, interferon-γ and TNF-α, and anti-inflammatory IL-10 being increased when compared to the control group. In conclusion, our results demonstrate that oxidative stress and inflammation occurs in UCD and probably contribute to the severe brain damage present in patients.

Epithelial-mesenchymal transition and cancer stem cells: A route to acquired cisplatin resistance through epigenetics in HNSCC.

Chemoresistance is associated with tumor recurrence, metastases, and short survival. Cisplatin is one of the most used chemotherapies in cancer treatment, including head and neck squamous cell carcinoma (HNSCC), and many patients develop resistance. Here, we established cell lines resistant to cisplatin to better understand epigenetics and biological differences driving the progression of HNSCC after treatment. Cisplatin resistance was established in CAL-27 and SCC-9 cell lines. Gene expression of HDAC1, HDAC2, SIRT1, MTA1, KAT2B, KAT6A, KAT6B, and BRD4 indicated the cisplatin activates the epigenetic machinery. Increases in tumor aggressiveness were detected by BMI-1 and KI-67 in more resistant cell lines. Changes in cellular shape and epithelial-mesenchymal transition (EMT) activation were also observed. HDAC1 and ZEB1 presented an opposite distribution with down-regulation of HDAC1 and up-regulation of ZEB1 in the course of chemoresistance. Up-regulation of ZEB1 and BMI-1 in patients with HNSCC is also associated with a poor response to therapy. Cancer stem cells (CSC) population increased significantly with chemoresistance. Down-regulation of HDAC1, HDAC2, and SIRT1 and accumulation of Vimentin and ZEB1 were observed in the CSC population. Our results suggest that in the route to cisplatin chemoresistance, epigenetic modifications can be associated with EMT activation and CSC accumulation which originate more aggressive tumors.

Worldwide prevalence of geographic tongue in adults: A systematic review and meta-analysis.

To identify the prevalence of geographic tongue in patients >18 years. A systematic literature review was performed in search of population-based observational studies. Searches were performed using five main databases: Embase, LILACS, PubMed, Scopus and Web of Science; and three gray literature sources: Google Scholar, ProQuest, and OpenGrey. In addition, a manual search in the reference list and consultation with experts on the topic studied were performed. Methodological quality was assessed using the Joanna Briggs Institute's checklist for prevalence studies. Ratio meta-analyses were performed using JAMOVI. Initially, 3046 studies were identified. After a two-phase selection, 11 studies were included for quantitative synthesis. Two studies were classified as of low methodological quality, five studies as of moderate quality, and four as of high quality. Two types of prevalence were analyzed: by period and point. Three studies were included in the period prevalence meta-analysis, and the prevalence was 3% (Confidence interval [CI]: 0.4%-5.5%, n = 9813). Eight studies were included in the point-prevalence meta-analysis, and the prevalence was 3% (CI: -0.2% to 5.5%, n = 10,967). Although there are phases of exacerbation and remission in geographic tongue, prevalence and period prevalence were similar. Approximately one in 30 adults has a geographic tongue.

Seropositivity for syphilis among Brazilian blood donors. A retrospective study 2015-2020.

INTRODUCTION: Syphilis is a transfusion-transmitted infection and the disease re-emerged in many countries, including Brazil, as a public health risk. OBJECTIVE: Evaluate the prevalence of positive serology in blood donations rejected by Hemobanco (Curitiba- PR) from January 2015 to December 2020, with special focus in syphilis. METHODOLOGY: In the studied period, we analyzed the number of blood donations discarded annually for each serological test performed on blood donors' samples, according to gender and donors age. RESULTS: Within the studied period, 134,741 blood donation were analyzed. 54.5 % of sample were male. Otherwise, it was observed a significant increase in the number of donations by females (P < 0.0001). There was an increase of 437 % in the prevalence of syphilis positive serology made by donors with ≥ 60 years. Besides that, it was noticed a significant increase in donations by aged people throughout these six years (P < 0.0001). The percentage of total blood donation deferred had a significant reduction, although it was observed an increase in the rate of discarded blood bags due to positive serology in the first 4 studied years. It was observed an increase of 20 % in positive syphilis serology. CONCLUSION: The greatest cause of discard of blood donations changed during the analyzed 5-years; there was an increase in seropositivity donations from donors with ≥ 60 years old. In 2015, Hepatitis B (0.8 %) was the most prevalent and in 2020, syphilis became more prevalent (0.82 %). The medical community should be aware of the rising number of cases of syphilis infection. There is an urgent need to implement actions against the dissemination of this disease.

Different Multidrug-Resistant Salmonella spp. Serovars Isolated from Slaughter Calves in Southern Brazil.

Bovines are carriers of Salmonella spp., a relevant foodborne pathogen, acting as contamination sources in slaughterhouses. Calves are prone to infection, and antimicrobial resistance may occur in such bacteria. This study aimed to determine the prevalence and virulence determinants of Salmonella spp. recovered from calves in the Rio Grande do Sul state, Brazil. Eighty-five calves' carcasses were evaluated (leather and veal meat). Thirteen Salmonella spp. isolates (8%) from 11 animals (13%) were obtained only from leather, indicating that contamination occurred before slaughter and that the meat was safe regarding this aspect. The serotypes S. Minnesota, S. Abony, S. Cerro, and S. Gafsa were identified, and all isolates were multidrug-resistant. The isolates had at least 19 virulence-related genes, and the blaOXA-48 resistance gene was detected in three (23%). The data suggest that treating infections caused by these bacteria may be difficult in animals from these farms and can also be an extended human health problem.

Critical appraisal of systematic reviews of intervention in dentistry published between 2019-2020 using the AMSTAR 2 tool.

Introduction The number of systematic reviews (SRs) in dentistry published each year has grown considerably, and they have been essential in clinical decision-making and health policy.Objective The objective is to critically appraise SRs of intervention in dentistry using the 'A Measurement Tool to Assess Systematic Reviews 2' (AMSTAR 2) tool published within one year.Methods A search in the Medline/PubMed database was performed. The SRs were identified in two phases. The first phase identified SRs of interventions in dentistry by title and abstract. In the second phase, the full text was read, applying the eligibility criteria. Three calibrated reviewers methodologically assessed all SRs identified using the AMSTAR 2 tool. Data were analysed descriptively, and SRs were grouped according to methodological quality as moderate/high and low/critically low. A logistic regression model was applied to explore the associations between methodological quality and the study's characteristics.Results Two hundred and twenty-two SRs were included. The methodological quality of the SRs included in this study were: critically low (56.8%), low (27.9%), moderate (14.4%) and high (0.9%), according to AMSTAR 2. There were no statistical differences between moderate/high and low/critically low methodological quality and publication year, continent, journal Impact Factor and dental speciality.Conclusion Less than 1% of recently published SRs in dentistry were classified with high methodological quality. We hope that this study will alert researchers about the need to improve the methodological quality of SRs.

The effects of levodopa in the spatiotemporal gait parameters are mediated by self-selected gait speed in Parkinson's disease.

In individuals with Parkinson's disease (PD), the medication induces different and inconsistent results in the spatiotemporal parameters of gait, making it difficult to understand its effects on gait. As spatiotemporal gait parameters have been reported to be affected by gait speed, it is essential to consider the gait speed when studying walking biomechanics to interpret the results better when comparing the gait pattern of different conditions. Since the medication alters the self-selected gait speed of individuals with PD, this study analysed whether the change in gait speed can explain the selective effects of l-DOPA on the spatiotemporal parameters of gait in individuals with PD. We analysed the spatiotemporal gait parameters at the self-selected speed of 22 individuals with PD under ON and OFF states of l-DOPA medication. Bayesian mediation analysis evaluated which gait variables were affected by the medication state and checked if those effects were mediated by speed changes induced by medication. The gait speed was significantly higher among ON compared with OFF medication. All the spatiotemporal parameters of the gait were mediated by speed, with proportions of mediation close to 1 (effect entirely explained by speed changes). Our results show that a change in gait speed better explains the changes in the spatiotemporal gait parameters than the ON-OFF phenomenon. As an implication for rehabilitation, our results suggest that it is possible to assess the effect of l-DOPA on improving motor symptoms related to gait disorders by measuring gait speed.

Compensatory control between the legs in automatic postural responses to stance perturbations under single-leg fatigue.

In response to sudden perturbations of stance stability, muscles of both legs are activated for balance recovery. In conditions that one of the legs has a reduced capacity to respond, the opposite leg is predicted to compensate by responding more powerfully to restore stable upright stance. In this investigation, we aimed to evaluate between-leg compensatory control in automatic postural responses to sudden perturbations in a situation in which plantar flexor muscles of a single leg were fatigued. Young participants were evaluated in response to a series of perturbations inducing forward body sway, with a focus on activation of plantar flexor muscles: lateral and medial gastrocnemii and soleus. Muscular responses were analyzed through activation magnitude and latency of muscular activation onset. For evaluation of balance and postural stability, we also analyzed the center of pressure and upper trunk displacement and weight-bearing asymmetry between the legs. Responses were assessed in three conditions: pre-fatigue, under single-leg fatigue, and following the recovery of muscular function. Results showed (a) compensation of the non-fatigued leg through the increased magnitude of muscular activation in the first perturbation under fatigue; (b) adaptation in the non-fatigued leg over repetitive perturbations, with a progressive decrement of muscular activation over trials; and (c) maintenance of increased muscular activation of the non-fatigued leg following fatigue dissipation. These findings suggest that the central nervous system is able to modulate the descending motor drive individually for each leg's muscles apparently based on their potential contribution for the achievement of the behavioral aim of recovering stable body balance following stance perturbations.

Prevalence of orofacial injuries in wheeled non-motor sports athletes: A systematic review and meta-analysis.

BACKGROUND/AIMS: As the popularity of sports activities grows, so do the number of sport-related injuries. Furthermore, sports that use equipment or vehicles that modify the speed of the player can present more serious injuries. The aim of this systematic review was to identify the overall prevalence of orofacial trauma in wheeled non-motor sports athletes. METHODS: The search strategy was applied in eight electronic databases (Embase, LILACS, Livivo, PEDro, PubMed, Scopus, SportDiscus, and Web of Science). Additionally, a complementary search of the gray literature (Google Scholar, OpenGrey, and ProQuest Dissertations & Theses Global), reference lists of included articles, and studies indicated by experts on the subject was done. The included articles were observational studies with sufficient data of orofacial trauma (type and anatomical site) in wheeled non-motor sport athletes, regardless of the competition level. Risk of bias was assessed by using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. The meta-analysis was performed using R Statistics software, and the strength of cumulative evidence was assessed by The Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: From 4042 identified studies, after the removal of duplicates and phase one of selection (title and abstracts screening), 251 studies remained for phase two (full-text screening). Five articles were finally included. One study was considered to have a low risk of bias and four had a moderate risk of bias. The cumulative prevalence of orofacial injuries in wheeled non-motor sport athletes was 21.7% (CI: 8.7-34.7; I2 :97.6%) and the prevalence of dental injuries in these sports was 7.5% (CI:4.3-10.7; I2 :61.9%). The certainty in cumulative evidence was considered to be very low. CONCLUSION: About 22% of the wheeled non-motor sport athletes have suffered orofacial injuries. The most prevalent type of injury was classified as dental trauma.

Instantaneous interjoint rescaling and adaptation to balance perturbation under muscular fatigue.

Adaptation of automatic postural responses (APR) to balance perturbations might be thought to be impaired by muscle fatigue, given the associated proprioceptive and effector deficits. In this investigation, we aimed to evaluate the effect of muscular fatigue on APR adaptation over repetitive balance perturbations through support base backward translations. APR adaptation was evaluated in three epochs: (a) pre-fatigue; (b) post-fatigue, immediately following fatigue of the plantiflexor muscles through isometric contractions and (c) post-recovery, 30 min after the end of fatiguing activity. Results showed the following: (a) Decreasing amplitudes of joints' maximum excursion over repetitive perturbations in the three fatigue-related epochs. (b) Modulation of joints' excursion was observed in the first trial in the post-fatigue epoch. (c) In the post-fatigue epoch, we found interjoint rescaling, with greater amplitude of hip rotation associated with reduced amplitude of ankles' rotation. (d) Amplitudes of ankles' rotation were similar between the post-fatigue and post-recovery epochs. These findings lead to the conclusions that adaptation of automatic postural responses over repetitive trials was effective under focal muscular fatigue; modulation of the postural response took place in the first perturbation under fatigue, and generalization of response characteristics from post-fatigue to post-recovery suggests that feedforward processes in APRs generation are affected by the recent history of postural responses to stance perturbations.

Automatic postural responses are scaled from the association between online feedback and feedforward control.

Generation of automatic postural responses (APRs) scaled to magnitude of unanticipated postural perturbations is required to recover upright body stability. In the current experiment, we aimed to evaluate the effect of previous postural perturbations on APR scaling under conditions in which the current perturbation is equal to or different from the previous perturbation load inducing unanticipated forward body sway. We hypothesized that the APR is scaled from the association of the current perturbation magnitude and postural responses to preceding perturbations. Evaluation was made by comparing postural responses in the contexts of progressive increasing versus decreasing magnitudes of perturbation loads. Perturbation was applied by unanticipatedly releasing a cable pulling the body backwards, with loads corresponding to 6%, 8% and 10% of body mass. We found that the increasing as compared to the decreasing load sequence led to lower values of (a) displacement and (b) velocity of center of pressure, and of activation rate of the muscle gastrocnemius medialis across loads. Muscular activation onset latency decreased as a function increasing loads, but no significant effects of load sequence were found. These results lead to the conclusion that APRs to unanticipated perturbations are scaled from the association of somatosensory feedback signaling balance instability with feedforward control from postural responses to previous perturbations.

High contextual interference in perturbation-based balance training leads to persistent and generalizable stability gains of compensatory limb movements.

Reactive responses to balance perturbations have been shown to be improved by training. This investigation aimed to compare the effects of block and random training perturbation schedules on stability gains of compensatory arm and leg movements in response to unpredictable large-magnitude balance perturbations. Perturbations were produced by means of sudden displacements of the support base, associating mode (rotation, translation, combined), direction, and velocity of platform motion. Healthy young participants were assigned to one of three groups: random, block, and control. For the random group, perturbation sequence was unpredictable. For the block group, each balance perturbation was repeated over blocks of four trials. Controls were tested only, serving as reference of first trial responses in the post-test. Evaluation was made through a scale rating stability of compensatory arm and leg movements (CALM). We probed immediate and persistence gains (1-week retention), in addition to generalizability to perturbations of higher velocity and to dual-tasking (mental subtraction). In the post-test both the block and random groups achieved higher leg and global scores in comparison with controls in the most challenging perturbations. In retention and transfer tests, results for the global score indicated higher values for the random than for the block and control groups. These results support the conclusion that high but not low contextual interference in perturbation-based balance training leads to enduring and generalizable increased stability gains of compensatory limb movements in response to unpredictable balance perturbations.

[Suicide and indigenous populations in Brazil: systematic reviewEl suicidio y los pueblos indígenas brasileños: revisión sistemática]. / Suicídio e povos indígenas brasileiros: revisão sistemática.

OBJECTIVE: To describe the frequency, characteristics, and factors contributing to suicide in indigenous populations in Brazil. METHOD: A systematic review of the literature was performed in PubMed, SciELO, PsycINFO, and LILACS. All population-based studies focusing on suicide among indigenous populations in Brazil were included. RESULTS: The search identified 111 articles, of which nine met the inclusion criteria. Three of these studies were performed in the Midwest and four in the North of Brazil, while two covered all Brazilian regions. The ethnic groups investigated were specified in three studies (Terena, Kadiweu, Guato, Ofaie-Xavante, Guarani, Guarani-Kaiowá, and Guarani-Nandeva). Suicide rates were highest among males, single individuals, those with 4 to 11 years of schooling, and those aged 15 to 24 years. Suicides occurred most often in the home and on weekends, mostly by hanging. The main risk factors for suicide identified in the articles were poverty, historical and cultural factors, poor wellbeing indicators, family disintegration, social vulnerability, and lack of life or future perspective. CONCLUSIONS: All the studies indicated the need to engage communities in developing strategies, considering their cosmovision and the social, historic, and cultural view of each ethnic group to minimize risk factors and reduce suicide rates.

OBJETIVO: Describir la frecuencia y las características del suicidio y sus factores contribuyentes en los pueblos indígenas brasileños. MÉTODO: Se realizó una revisión sistemática de la bibliografía a partir de las bases de datos PubMed, SciELO, PsycINFO y LILACS. Se incluyeron estudios de base poblacional enfocados en el suicidio en las poblaciones indígenas en el territorio brasileño. RESULTADOS: En la búsqueda se encontraron 111 artículos, de los cuales nueve se ciñeron a los criterios de inclusión. Se realizaron tres estudios en la región centro oeste y cuatro en la región norte, además de otros dos que abarcaron todas las regiones de Brasil. En tres estudios se citaron todas las siete etnias estudiadas (Terena, Kadiweu, Guato, Ofaie-Xavante, Guaraní, Guaraní-Kaiowá y E-Nandeva). En los estudios se demostró una mayor tasa de mortalidad por suicidio en personas solteras del sexo masculino, con 4 a 11 años de escolaridad, en el grupo de 15 a 24 años de edad, en el domicilio y en los fines de semana, principalmente por el método de ahorcamiento. Los principales factores de riesgo de suicidio fueron la pobreza, factores históricos y culturales, el índice de bienestar bajo, la desintegración de las familias, la vulnerabilidad social, y la falta de sentido de la vida y del futuro. CONCLUSIONES: Todos los estudios indicaron la necesidad de formular estrategias junto con las comunidades, dentro del marco de su cosmovisión y de los aspectos sociales, históricos y culturales de cada etnia, con el fin de reducir al mínimo los factores de riesgo y la tasa de mortalidad por suicidio.

Surface treatments to improve the repair of acrylic and bis-acryl provisional materials.

PURPOSE: To evaluate the in vitro effects of the Composite Primer and different surface treatments on the shear bond strength (SBS) of acrylic and bis-acryl repairs with resin composite (RC). METHODS: Acrylic (Alike) and bis-acryl (Protemp 4) blocks were prepared. Surface roughness was standardized (0.16 µm) and grit blasting was applied to half of the samples. Blocks were divided randomly into groups according to surface treatment [methyl methacrylate monomer (MMA) for 180 seconds or bonding agents (Composite Primer and Scotchbond Multi Purpose), applied alone or following MMA]. Two consistencies of RC [ regular (Filtek Z350XT and Solare composite) or flowable (Filtek Z350XT flowable and G-aenial flowable composite) ] were used to test bond repair. Cylinders (2 mm diameter) of each RC (n= 10/group) were attached to the block surface, and SBS was measured using a universal testing machine at 0.5 mm/minute. Failure (adhesive, cohesive or mixed) was assessed under ×3.5 magnification. SBS data were analyzed using factorial ANOVA, followed by Tukey post-hoc, and Weibull moduli estimation (α = 0.05). RESULTS: The highest SBS, Weibull modulus (m) and scale parameter (σ0) were found in combined use of MMA and bonding agents (P< 0.001), regardless of the substrate, RC consistency or brand. The use of the Composite Primer and flowable RC also increased SBS (P< 0.001). Significant interaction between surface treatment and RC consistency was observed for the PMMA substrate (P< 0.001). Sandblasting did not influence SBS (P> 0.05). Adhesive failure was most prevalent (93.5%) and SBS values were significantly higher in mixed fractures (19.2± 3.8 MPa) compared to the adhesive ones (9.7± 6.0 MPa) (P< 0.001). No cohesive fracture was observed. CLINICAL SIGNIFICANCE: Composite Primer improved the adhesion of acrylic and bis-acryl repairs, especially when a flowable composite was used. When such product is not available, the combined use of MMA and a bonding agent is necessary, increasing the number of clinical steps, cost, and time required.

Determination of statin drugs in hospital effluent with dispersive liquid-liquid microextraction and quantification by liquid chromatography.

Statins are classified as being amongst the most prescribed agents for treating hypercholesterolaemia and preventing vascular diseases. In this study, a rapid and effective liquid chromatography method, assisted by diode array detection, was designed and validated for the simultaneous quantification of atorvastatin (ATO) and simvastatin (SIM) in hospital effluent samples. The solid phase extraction (SPE) of the analytes was optimized regarding sorbent material and pH, and the dispersive liquid-liquid microextraction (DLLME), in terms of pH, ionic strength, type and volume of extractor/dispersor solvents. The performance of both extraction procedures was evaluated in terms of linearity, quantification limits, accuracy (recovery %), precision and matrix effects for each analyte. The methods proved to be linear in the concentration range considered; the quantification limits were 0.45 µg L-1 for ATO and 0.75 µg L-1 for SIM; the matrix effect was almost absent in both methods and the average recoveries remained between 81.5-90.0%; and the RSD values were <20%. The validated methods were applied to the quantification of the statins in real samples of hospital effluent; the concentrations ranged from 18.8 µg L-1 to 35.3 µg L-1 for ATO, and from 30.3 µg L-1 to 38.5 µg L-1 for SIM. Since the calculated risk quotient was ≤192, the occurrence of ATO and SIM in hospital effluent poses a potential serious risk to human health and the aquatic ecosystem.

Antiepileptic drug prophylaxis in primary brain tumor patients: is current practice in agreement to the consensus?

The role of antiepileptic drugs (AED) prophylaxis in primary brain tumor (PBT) seizure-naïve patients remains unclear. Additionally, AED are associated with severe side effects, negative impact on cognition and drug interactions. Little is known about current practice regarding prophylactic AED use in PBT. We investigated its use in a tertiary care cancer center. We reviewed medical records of 260 patients registered in our center between 2008 and 2012, focusing on prophylactic AED use. A descriptive analysis was performed with SPSS IBM version 20.0. Median age was 44.5 years (11-83). Most patients had ECOG PS ≤1 (76.4 %). Among 141 seizure-naïve patients, 70.2 % received an AED as primary prophylaxis (PP). Most commonly used drugs as PP were phenytoin (85.9 %), carbamazepine (6.1 %) and phenobarbital (5.1 %). In only 14 patients (14.1 %) AEDs were eventually discontinued, in a median time of 5.9 months (1.1-76.8 m). AED were used as PP in 60 % of low-grade gliomas, 73.3 % of anaplastic gliomas and 93.9 % of glioblastoma patients. Twenty-seven patients (27.3 %) on PP presented seizures, generally associated with tumor progression. Of the 42 seizure-naïve patients not receiving AED prophylaxis, only two presented seizures, which occurred during or within the first week post-radiotherapy. In this cross-sectional study, prophylactic AED use in PBT was extremely high. Postoperatively, AED were discontinued in a minority of patients, mostly after a prolonged period. Current prophylactic AED use patterns in PBT are not in accordance with established guidelines.

Long-term results of the Modified Thal procedure in patients with chagasic megaesophagus.

BACKGROUND: Chagas disease is a serious public health issue in South and Central America due to its high prevalence, morbidity, and mortality. The esophageal form of the disease leads to achalasia and consequent megaesophagus. In advanced or recurrent cases of megaesophagus, there is no consensus for which of three established techniques-the Serra-Dória procedure, subtotal esophagectomy, or Modified Thal cardioplasty-is best. Very few studies have investigated the average efficacy and long-term outcomes of the Thal procedure. The present study sought to bridge this gap. METHODS: The Modified Thal procedure was performed in 29 patients at Hospital Universitário de Brasília between 1998 and 2008. All underwent clinical and nutritional evaluation, upper gastrointestinal endoscopy (UDE) with chromoscopy, esophageal manometry, and 24-h pH monitoring. RESULTS: Overall, 86 % experienced resolution of all symptoms after surgery. Most patients were classified as Visick grade I, II, or III. The average body mass index was 22.7 kg/m(2). UDE showed normal mucosa in 76 % of patients, and 11 % had unstained areas on chromoscopy. Esophageal manometry demonstrated incomplete lower esophageal sphincter (LES) relaxation in 50 % of patients, complete LES relaxation in 21 %, and no LES relaxation in 29 %. All showed complete relaxation of the upper esophageal sphincter. On 24-h pH monitoring, reflux was pathological in 50 % of patients. CONCLUSIONS: Overall, the modified Thal procedure improved symptoms-namely, dysphagia to liquids with resulting weight loss and malnutrition-in patients with megaesophagus. No correlations were found between clinical complaints, endoscopic findings, and degree of manometric abnormality in these patients.

Synthesis and biological evaluation of novel 3-alkylpyridine marine alkaloid analogs with promising anticancer activity.

Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA) analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c) were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.