Would frontal midline theta indicate cognitive changes induced by non-invasive brain stimulation? A mini review.

To the best of our knowledge, neurophysiological markers indicating changes induced by non-invasive brain stimulation (NIBS) on cognitive performance, especially one of the most investigated under these procedures, working memory (WM), are little known. Here, we will briefly introduce frontal midline theta (FM-theta) oscillation (4-8 Hz) as a possible indicator for NIBS effects on WM processing. Electrophysiological recordings of FM-theta oscillation seem to originate in the medial frontal cortex and the anterior cingulate cortex, but they may be driven more subcortically. FM-theta has been acknowledged to occur during memory and emotion processing, and it has been related to WM and sustained attention. It mainly occurs in the frontal region during a delay period, in which specific information previously shown is no longer perceived and must be manipulated to allow a later (delayed) response and observed in posterior regions during information maintenance. Most NIBS studies investigating effects on cognitive performance have used n-back tasks that mix manipulation and maintenance processes. Thus, if considering FM-theta as a potential neurophysiological indicator for NIBS effects on different WM components, adequate cognitive tasks should be considered to better address the complexity of WM processing. Future research should also evaluate the potential use of FM-theta as an index of the therapeutic effects of NIBS intervention on neuropsychiatric disorders, especially those involving the ventral medial prefrontal cortex and cognitive dysfunctions.

ß1- and ß1/ß2-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens.

6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective ß-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective ß1- and ß1/ß2-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective ß1-adrenergic receptor antagonists atenolol (0.1 and 1 µï»¿M), betaxolol (1 µï»¿M), and metoprolol (1 µï»¿M) and the unselective ß1/ß2-adrenergic receptor antagonists propranolol (1 and 10 µï»¿M) and pindolol (10 µï»¿M) caused significant rightward shifts of the concentration-response curve to 6-ND (pA2 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective ß1- and ß1/ß2-adrenergic receptor antagonists at a higher concentration (atenolol 1 µï»¿M, betaxolol 1 µï»¿M, metoprolol 1 µï»¿M, propranolol 10 µï»¿M, and pindolol 10 µï»¿M) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective ß1-adrenoceptor agonist RO-363, the selective ß2-adrenoceptor agonist salbutamol, and the selective ß3-adrenoceptor agonist mirabegron, up to 300 µï»¿M, had no effect on the RIEVD tone. The results demonstrate that ß1- and ß1-/ß2-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.

Endothelium-derived dopamine modulates EFS-induced contractions of human umbilical vessels.

Electrical field stimulation (EFS) induces contractions of both snake aorta and human umbilical cord vessels (HUCV) which were dependent on the presence of the endothelium. This study aimed to establish the nature of the mediator(s) responsible for EFS-induced contractions in HUCV. Rings with or without endothelium from human umbilical artery (HUA) or vein (HUV) were mounted in organ bath chambers containing oxygenated, heated Krebs-Henseleit's solution. Basal release of dopamine (DA), noradrenaline, and adrenaline was measured by LC-MS-MS. Cumulative concentration-response curves were performed with dopamine in the absence and in the presence of L-NAME or of dopamine antagonists. EFS studies were performed in the presence and absence of L-NAME, the α-adrenergic blockers prazosin and idazoxan, and the dopamine antagonists SCH-23390 and haloperidol. Tyrosine hydroxylase (TH) and dopa-decarboxylase (DDC) were studied by immunohistochemistry and fluorescence in situ hybridizations. Basal release of dopamine requires an intact endothelium in both HUA and HUV. TH and DDC are present only in the endothelium of both HUA and HUV as determined by immunohistochemistry. Dopamine induced contractions in HUA only in the presence of L-NAME. Dopamine-induced contractions in HUV were strongly potentiated by L-NAME. The EFS-induced contractions in both HUA and HUV were potentiated by L-NAME and inhibited by the D2-like receptor antagonist haloperidol. The α-adrenergic antagonists prazosin and idazoxan and the D1-like receptor antagonist SCH-23390 had no effect on the EFS-induced contractions of HUA and HUV. Endothelium-derived dopamine is a major modulator of HUCV reactivity in vitro.

Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

ABSTRACT Introduction and objective: In this study, we evaluated the influence of the transcript type on hematological and clinical parameters, as well as the event-free survival of 50 patients in the Chronic myeloid leukemia chronic phase. Methods: We reviewed the medical records of 55 patients with Chronic myeloid leukemia. The eligibility criteria were based on the availability of hematological and clinical baseline data in the medical records. Data on BCR-ABL transcripts were obtained from medical records. Results: Eighteen patients (36%) had the b2a2 transcript, 24 (48%) had b3a2 and 8 (16%) had b2a2/b3a2. The median platelet count for transcripts b2a2, b3a2 and b2a2/b3a2 was 320.65 × 103/L, 396 × 103/L, and 327.05 × 103/L, respectively (p = 0.896). We could not find any differences in relation to the other hematological parameters, when compared to the transcript type. Comparison between spleen and liver size and type of transcript did not differ inside the groups (p = 0.395 and p = 0.647, respectively) and the association between risk scores and transcript type did not show statistical significance (p > 0.05). The 21-month probability for event-free survival was 21%, 48% and 66% for the transcripts b2a2, b3a2 and b2a2/b3a2 respectively (p = 0.226) Conclusion: We conclude that the expression BCR-ABL transcripts have no influence on hematological, clinical and event-free survival parameters of patients in the Chronic myeloid leukemia chronic phase.

Parenting program versus telephone support for Mexican parents of children with acquired brain injury: A blind randomized controlled trial.

INTRODUCTION: Acquired brain injury (ABI) during childhood typically causes behavior problems in the child and high levels of stress in the family. The aims of this study are: (1) to investigate the effectiveness and feasibility of a parenting intervention in improving behavior and self-regulation in Mexican children with ABI compared to telephone support; (2) to investigate the effectiveness and feasibility of a parenting intervention in improving parenting skills, parent self-efficacy and decreasing parental stress in parents of children with ABI compared to telephone support. Our secondary aims are (1) to explore the impact that parent characteristics have on the intervention outcomes; (2) to investigate if changes are maintained 3 months after the intervention. METHODS: The research design is a blind randomized controlled trial (RCT). Eligible participants include children with a diagnosis of ABI, between 6 and 12 years of age, and their parents. Sixty-six children and their parents will be randomly allocated to either a parenting program group or telephone support group. The parenting program involves six face-to-face weekly group sessions of 2.5 h each. Participants in the control group receive an information sheet with behavioral strategies, and six weekly phone calls, in which strategies to improve academic skills are provided. Children and their parents are evaluated by blind assessors before the intervention, immediately after the intervention and 3-months post-intervention. DISCUSSION: This study will be the first to evaluate the efficacy and feasibility of a parenting program for Mexican parents of children with ABI. TRIAL IDENTIFIER: ACTRN12617000360314.

Cutaneous melanoma in children and adolescents: the Italian rare tumors in pediatric age project experience.

OBJECTIVE: To describe a series of cutaneous melanoma in children collected by the Italian Rare Tumors in Pediatric Age project. STUDY DESIGN: From 2000 to 2012, 54 patients younger than 18 years of age were prospectively registered and treated at 12 Italian pediatric centers on the basis of the same diagnostic/therapeutic recommendations and with the same forms to record clinical data. RESULTS: Considering the estimated annual incidence in Italy, the registered cases accounted for 30% of those expected in children and 10% of adolescents. Clinically, 47% of the tumors were amelanotic and 81% were raised, 39% of cases had tumor thickness >2 mm, and 36% had lymph node involvement. For the whole series, 5-year event-free survival and overall survival rates were 75.2% and 84.6%, respectively. Patient survival correlated with tumor stage and ulceration. No relapses were recorded for T1-2 (thickness <2 mm), N0, and stage 0-I-II cases. CONCLUSION: We suggest that the variables influencing survival in children with melanoma are the same as for adults, the clinical approach used in adults is feasible in children, and pediatric cases are more likely to have advanced disease at diagnosis but similar survival. New effective drugs are needed for advanced disease, and biological studies and international cooperative schemes are warranted.

Expression of KLF4 is a predictive marker for survival in pediatric Burkitt lymphoma.

Krüppel-like factor 4 (KLF4) is expressed in a variety of tissues with diverse physiological functions and activities. KLF4 can also function as a tumor suppressor or an oncogene, depending on the cellular context. Its role in hematological malignancies is controversial. This study examined the expression levels of KLF4 by immunohistochemistry in 73 pediatric non-Hodgkin lymphomas (NHLs) in a tissue microarray and also on several B-NHL cell lines. Elevated levels of KLF4 expression were detected in 66% of lymphoma cases and were more frequent in the Burkitt lymphoma (p = 0.05) subtype. There was a significant predictive power for outcome with low KLF4 expression, predicting a favorable overall survival compared to high levels. Multivariate analyses confirmed the association of KLF4 expression with unfavorable overall survival (p < 0.005). These findings were consistent with analyses in existing NHL microarray datasets. The present findings revealed that KLF4 is overexpressed in Burkitt pediatric lymphoma and is a potential biomarker for inferior overall survival.

Desenvolvimento e validação de um método por CLAE-EM/EM para determinação de PGE2 e PGD2 em meio de cultivo celular e avaliação da recuperação das prostaglandinas utilizando diferentes condições na extração em fase sólida / Development and validation of HPLC-MS/MS method to determine PGE2 and PGD2 in cell culture medium and assessment of recovery of the prostaglandins by solid phase extraction under various conditions

Tradicionalmente, estas prostaglandinas são quantificadas por técnicas de imuno-ensaio, que apresentam diversas desvantagens. Estes metabólitos são isômeros estruturais, e dessa forma é necessário o uso de técnicas de detecção seletivas, como cromatografia líquida acoplada à espectrometria de massas sequencial (CLAE-EM/EM). Para a extração de prostaglandinas de matrizes complexas, destaca-se a extração em fase sólida (EFS), que otimizada, fornece excelentes taxas de recuperação. O objetivo deste trabalho foi desenvolver e validar um método rápido por CLAE-EM/EM, para análise simultânea de PGE2 e PGD2 de meio de cultivo celular e avaliar a eficiência de extração em diferentes condições de EFS, em relação ao método proposto pelo fabricante dos cartuchos. A separação ocorreu com coluna de fase reversa (C18, 150mm x 2.1mm, 5μm) eluída no modo gradiente com acetonitrila e água (0,1% AFO). Dez condições diferentes de EFS foram testadas. O método desenvolvido foi adequado para a análise simultânea de PGE2 e PGD2 , apresentando resolução de ~1,5 entre os picos e corrida de 11 minutos. LD da ordem de 0,5 ng/mL e LQ de 1,0 ng/mL foram obtidos para ambos os analitos. A linearidade de PGE2 e PGD2 apresentou r>0,99. Variações inferiores a 6,51% e 5,93% foram encontradas para repetibilidade e precisão intermediária, respectivamente. Foi possível diminuir perdas durante a EFS e aumentar a recuperação dos analitos. A condição que ofereceu melhor eficiência de extração aumentou o rendimento em 181% para PGE2 e 323% para PGD2 , em relação ao método proposto pelo fabricante.

PGE2 and PGD2 are very important pro-inflammatory mediators. Traditionally, these prostaglandins are estimated by immunoassay techniques, which have several disadvantages. Since these metabolites are structural isomers, it is necessary to use selective detection techniques, such as liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). For the extraction of prostaglandins from complex matrices, solid phase extraction (SPE) is an outstanding method that can be optimized to provide excellent recovery. The aim of this study was to develop and validate a rapid method for the simultaneous analysis of PGE2 and PGD2 in cell culture medium by HPLC-MS/MS and to assess the extraction efficiency of SPE under various conditions, compared to the generic method proposed by the manufacturer of the cartridges. The analytes were separated on a reversed-phase column (C18, 150mm x 2.1mm, 5μm), eluted in a gradient of acetonitrile and water (0.1% formic acid). Ten different conditions for SPE were tested. The method was suitable for the simultaneous analysis of PGE2 and PGD2 , showing a resolution of ~1.5 between the peaks and a run time of 11 minutes. LOD of 0.5 ng/mL and LOQ of 1.0 ng/mL were recorded for both analytes. The linearity of the analytical curves for both PGE2 and PGD2 showed r>0.99. Variations of less than 6.51% and 5.93% were found for repeatability and intermediate precision, respectively. It was possible to reduce the losses during SPE and enhance the recovery of the analytes. The condition affording the best extraction efficiency increased the yield by 181% for PGE2 and 323% for PGD2 , relative to the method proposed by the manufacturer.

Validación de uaa metodología para la determinaión de carbofuran en suelos meddiante cromatografía líquida de alta eficiencia con detección ultravioleta (clar-uv) / Validation ofan analytical method for carbofuran determinatin on soils by hhigh performance liquid chromatography with uv detection (hplc-uv) / Validação de um metodologia paa determinação do carbofurano em solos por crommatografia líquida da alta eficiência com detecção ultravioleta (clar-vv)

Se validó una metodología analítica que permite cuantificar residuos de carbofuran en muestras de suelo. La extracción del plaguicida desde la matriz se realizó mediante agitación mecánica empleando acetato de etilo como solvente, los extractos obtenidos se sometieron a extracción en fase sólida (EFS) utilizando cartuchos C18, finalmente, la determinación y cuantificación del carbofuran se llevó a cabo mediante cromatografía líquida de alta eficiencia con detección ultravioleta (CLAR-UV) a una longitud de onda de 205 nm. La metodología validada es específica y selectiva para el carbofuran, lineal en el rango desde 0,47 hasta 2,36 mgKg-1, precisa con un coeficiente de variación típico (CVtip) de 10,78%; exacta brindando un porcentaje de recuperación para la metodología global (porcentaje de R) equivalente a 98,25±3,97% y sensible con límites de detección y cuantifica-ción de 0,045 y 0,149 mgKg-1, respectivamente. También se verificó la robustez del método. Se analizaron dos muestras de suelo dedicados al cultivo de café, y se encontraron residuos de carbofuran durante los primeros 30 días después de su aplicación.

An analytic method was validated to quantify Carbofuran residues in soil samples. The pesticides were extracted from the matrix by mechanic stirring, using ethyl acetate as a solvent. These extracts were cleaned by using cartridges C18. The determination and quantification of Carbofuran was made by high performance liquid chromatography with ultraviolet detection (HPLC-UV). The wavelength was 205 nm. The validated method is specific and selective for Carbofuran, is linear in the range from 0.47 to 2.36 mg kg-1, is accurate with a typical variation coefficient of 10.78%, is exact with recovering percentage (% R) equivalent to 98.25±3.97% and sensitive with detection and quantification limits since 0.045 and 0.149 mg kg-1 respectively. The robustness of the method was recognized. Two samples from soil of coffee cultivation were analyzed. Residues ofCarbofuranwerefoundduringthe first thirty days after application. Two samples of soil coffee were analyzed finding residues of carbofuran during the first thirty days after application.

Neste artigo validou-se uma metodologia analítica que quantifica resíduos de carbo-furano em amostras de solo. Por agitação mecânica se extraíram pesticidas da matriz, utilizando acetato de etilo como solvente. Os extratos obtidos foram submetidos à extração em fase sólida (EFS) com cartuchos de C18. Em seguida, a identificação e quantificação de Carbofuran foi realizada por cromatografia líquida de alta eficiência com detecção ultravioleta (CLAE-UV). A longitude de onda foi 205 nm. A metodologia validada é específica e seletiva para car-bofuran; linear no intervalo de 0,47-2,36 mgkg-1, cocomumcoeficientedevariação (C. Vtip) típico de 10,78%, fornecendo uma taxa de recuperação precisa da meto-dologiaglobal(R%)equivalentea98,25± 3,97%. Os limites de sensibilidade de detecção e quantificação são 0,045 e 0,149 mg kg-1, respectivamente. Verificou-se também a robustez do método. Analisadas duas amostras de terra dedicada ao cultivo do café, se encontraram resíduos de carbofuran nos trinta primeiros dias após aplicá-lo.