LQFM289: Electrochemical and Computational Studies of a New Trimetozine Analogue for Anxiety Treatment.

This study employs electrochemical and Density Functional Theory (DFT) calculation approaches to investigate the potential of a novel analogue of trimetozine (TMZ) antioxidant profile. The correlation between oxidative stress and psychological disorders indicates that antioxidants may be an effective alternative treatment option. Butylatedhydroxytoluene (BHT) is a synthetic antioxidant widely used in industry. The BHT-TMZ compound derived from molecular hybridization, known as LQFM289, has shown promising results in early trials, and this study aims to elucidate its electrochemical properties to further support its potential as a therapeutic agent. The electrochemical behavior of LQFM289 was investigated using voltammetry and a mechanism for the redox process was proposed based on the compound's behavior. LQFM289 exhibits two distinct oxidation peaks: the first peak, Ep1a ≈ 0.49, corresponds to the oxidation of the phenolic fraction (BHT), and the second peak, Ep2a ≈ 1.2 V (vs. Ag/AgCl/KClsat), denotes the oxidation of the amino group from morpholine. Electroanalysis was used to identify the redox potentials of the compound, providing insight into its reactivity and stability in different environments. A redox mechanism was proposed based on the resulting peak potentials. The DFT calculation elucidates the electronic structure of LQFM289, resembling the precursors of molecular hybridization (BHT and TMZ), which may also dictate the pharmacophoric performance.

Electroanalytical Enzyme Biosensor Based on Cordia superba Enzyme Extract for the Detection of Phytomarkers in Kombucha.

Antioxidants are responsible for many beneficial health effects and are highly present in natural products, such as kombucha. Biosensors' development targeting antioxidants and phytomarkers are an active research field. This work aimed to propose a voltammetric polyphenolxidase (Cordia superba) biosensor for catechin and total phenolic compounds quantification in kombucha samples. Optimizations were performed on the biosensor of Cordia superba to improve the accuracy and selectivity, such as enzyme-substrate interaction time, analytical responses for different patterns and signal differences with the carbon paste and modified carbon paste electrode. Kombucha probiotic drink samples were fermented for 7 to 14 days at a controlled temperature (28 ± 2 °C). A linear curve was made for catechin with a range of 10.00 to 60.00 µM, with a limit of detection of 0.13 µM and limit of quantification of 0.39 µM. The biosensor proposed in this work was efficient in determining the patterns of phenolic compounds in kombucha.

New prognostic markers revealed by RNA-Seq transcriptome analysis after MYC silencing in a metastatic gastric cancer cell line.

MYC overexpression is considered a driver event in gastric cancer (GC), and is frequently correlated with poor prognosis and metastasis. In this study, we evaluated the prognostic value of genes upregulated by MYC in patients with GC. Metastatic GC cells (AGP01) characterized by MYC amplification, were transfected with siRNAs targeting MYC. RNA-seq was performed in silenced and non-silenced AGP01 cells. Among the differentially expressed genes, CIAPIN1, MTA2, and UXT were validated using qRT-PCR, western blot, and immunohistochemistry in gastric tissues of 213 patients with GC; and their expressions were correlated with clinicopathological and survival data. High mRNA and protein levels of CIAPIN1, MTA2, and UXT were strongly associated with advanced GC stages (P < 0.0001). However, only CIAPIN1 and UXT gene expressions were able to predict distant metastases in patients with early-stage GC (P < 0.0001), with high sensitivity (> 92%) and specificity (> 90%). Overall survival rate of patients with overexpressed CIAPIN1 or UXT was significantly lower (P < 0.0001). In conclusion, CIAPIN1 and UXT may serve as potential molecular markers for GC prognosis.

Voltammetric determination of tartaric acid in wines by electrocatalytic oxidation on a cobalt(II)-phthalocyanine-modified electrode associated with multiway calibration.

The electrocatalytic oxidation of tartaric acid on a carbon paste electrode modified with cobalt (II)-phthalocyanine was demonstrated and applied to the development of a highly sensitive, simple, fast and inexpensive voltammetric sensor to determine tartaric acid. The electrochemical behavior of the modified electrode was investigated by cyclic and square wave voltammetry, and the effect of experimental variables, such as dispersion and loading of cobalt (II)-phthalocyanine, together with optimum conditions for sensing the analyte by square wave voltammetry were assessed. In addition, the absence of a significant memory effect combined with the ease of electrode preparation led to the development of a sensitive and direct method to determine tartaric acid in wines. Interferences from other low molecular weight organic acids commonly present in wines were circumvented by using a multiway calibration technique, successfully obtaining the second order advantage by modeling voltammetric data with unfolded partial least square with residual bilinearization (U-PLS/RBL). A linear response range between 10 and 100 µmol L-1 (r = 0.9991), a relative prediction error of 4.55% and a recovery range from 96.41 to 102.43% were obtained. The proposed method is non-laborious, since it does not use sample pretreatment such as filtration, extraction, pre-concentration or cleanup procedures.

Report of IRPA task group on the impact of the eye lens dose limits.

In 2012 IRPA established a task group (TG) to identify key issues in the implementation of the revised eye lens dose limit. The TG reported its conclusions in 2013. In January 2015, IRPA asked the TG to review progress with the implementation of the recommendations from the early report and to collate current practitioner experience. This report presents the results of a survey on the view of the IRPA professionals on the new limit to the lens of the eye and on the wider issue of tissue reactions. Recommendations derived from the survey are presented. This report was approved by IRPA Executive Council on 31 January 2017.

Estimation of genetic parameters for test-day milk yield in first calving buffaloes / Estimación de parámetros genéticos para producción de leche en el día de control en búfalas de primer parto / Estimação de parâmetros genéticos para produção do leite no dia do controle em búfalas de primeiro parto

Background: the milk yield records measured along lactation provide an example of repeated measures; the random regression models are an appealing approach to model repeated measures and to estimate genetic parameters. Objective: to estimate the genetic parameters by modeling the additive genetic and the residual variance for test-day milk yield in first calving buffaloes. Methods: 3,986 test-day data from 1,246 first lactations of crossbred buffalo daughters of 23 sires and 391 dams between 1997 and 2008 from five farms were used. The model included the genetic and permanent environment additive as the random effect and the contemporary group (year, month of test-day) and age at calving as covariable (linear) fixed effects. The fixed (third order) and random (third to ninth order) regressions were obtained by Legendre polynomials. The residual variances were modeled with a homogeneous structure and various heterogeneous classes. The variance components were estimated using the WOMBAT statistical program (Meyer, 2006). Results: according to the likelihood ratio test, the best model included four variance classes, considering Legendre polynomials of the fourth order for permanent environment and additive genetic effects. The heritabilities estimates were low, varying from 0.0 to 0.14. The estimates of genetic correlations were high and positive among PDC1 and PDC8, except for PCD9, which was negative. This indicates that for any of the selection criteria adopted, the indirect genetic gain is expected for all lactation curves, except for PCD9. Conclusion: heterogeneity of residual variances should be considered in models whose goal is to examine the alterations of variances according to day of lactation.

Antecedentes: los registros de producción de leche medidos a lo largo de la lactancia son un ejemplo de medidas repetidas, los modelos de regresión aleatoria presentan un enfoque atractivo para modelar medidas repetidas y para estimar parámetros genéticos. Objetivo: estimar parámetros genéticos a través de la modelación de la varianza genética y residual para producción de leche en el día de control en búfalas de primer parto. Métodos: fueron analizados 3986 controles de producción de leche en la primera lactancia de 1246 búfalas, hijas de 391 hembras y 23 toros, durante los años 1997 hasta 2008 en 5 fincas. El modelo incluyó como efectos aleatorios genético aditivo y de ambiente permanente, como efectos fijos grupo contemporáneo compuesto por mes, año de control y la covariable de la edad de la búfala al parto (lineal). Las regresiones fijas (3er orden) y aleatorias (3er a 9no orden) fueron obtenidas mediante polinomios de Legendre. Las varianzas residuales fueron modeladas con una estructura homogénea y varias clases heterogéneas. Los componentes de varianza fueron estimados utilizando el programa WOMBAT. Resultados: de acuerdo con la prueba de la razón de verosimilitud, el mejor modelo fue con 4 clases de varianzas residuales, siendo considerado un polinomio de Legendre de cuarto orden para el efecto de ambiente permanente y genético aditivo. Las heredabilidades fueron bajas, variando desde 0,00 hasta 0,14. Las correlaciones genéticas fueron altas y positivas entre los PDC1 a PDC8, excepto en el PDC9 que fue negativo con respecto a los demás controles. Conclusiones: es necesario considerar la heterogeneidad de varianzas residuales en los modelos estudiados, con el fin de modelar los cambios en las variaciones respecto a los días en lactancia.

Antecedentes: os registros da produção do leite medidos ao longo da lactação, apresentam um exemplo de medidas repetidas. Os modelos de regressão aleatória apresentam abordagem atraente para modelar medidas repetidas e estimar parâmetros genéticos. Objetivo: estimar parámetros genéticos mediante a modelação das variâncias genéticas e residual da produção do leite no dia do controle em búfalas de primeiro parto. Métodos: foram analisados 3986 controles de produção de leite em primeiras lactações de 1246 búfalas, filhas de 391 fêmeas e 23 touros, entre 1997 e 2008 em 5 fazendas. No modelo foram incluídos como efeitos aleatórios o genético aditivo e ambiente permanente, e como fixos o grupo contemporâneo (mês e ano de controle) e a covariável a idade da búfala ao parto (Lineal). As regressões fixas (3° ordem) e aleatórias (3° a 9° ordem) foram obtidas mediante polinômios ortogonais de Legendre. As variâncias residuais foram modeladas mediante estruturas homogêneas e diferentes classes heterogêneas. Os componentes de variância foram estimadas mediante o software WOMBAT. Resultados: de acordo com a prova da máxima verossimilhança, o melhor modelo foi com 4 classes de variâncias residuais, sendo considerado polinômios de Legendre de quarto ordem para o efeito de ambiente permanente e genético aditivo. As herdabilidades foram baixas, variando desde 0,00 até 0,14. As correlações genéticas foram altas e positivas entre o PDC1 e PDC8, a exceção do PDC9 que apresentou valores negativos com respeito aos outros controles. Conclusões:é necessário considerar heterogeneidade de variâncias nos modelos estudados, tentando modelar as mudanças nas variações respeito aos dias em lactação.

Acute toxicity and environmental risk of teflubenzuron to Daphnia magna, Poecilia reticulata and Lemna minor in the absence and presence of sediment.

This study aimed to estimate the acute toxicity of teflubenzuron (1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea) (TFB) for Daphnia magna, Lemna minor and Poecilia reticulata, in the absence and presence of sediment; evaluate the effect of sediment on the TFB bioavailability; and to classify this insecticide according to its environmental poisoning risk for agricultural and aquaculture uses. The tests of TFB acute toxicity were conducted in static system in a completely randomized design with increasing TFB concentrations, and a control group. The TFB has been classified according to the estimated values of EC50 and LC50 by its acute toxicity and environmental risk. The sediment significantly reduced toxicity and bioavailability of TFB in water column. Therefore, the insecticide can be classified as being highly toxic to Daphnia magna, which means the agricultural and aquacultural uses of TFB pose a high risk of environmental toxicity to non-target organisms. However, it was practically non-toxic to L. minor and P. reticulata.

Asthma is not a common cause of severe chronic respiratory failure in non-smokers: ALOT study.

BACKGROUND: Little is known about the long-term natural history of asthma and the long-term clinical and functional consequences in non-smoking patients. From a functional point of view, non-smoking asthmatic patients may have a significantly greater decline in forced expiratory volume in one second (FEV1) compared with non-asthmatic subjects and may develop chronic irreversible (fixed) airflow limitation. This has been related to the physiological consequences of chronic airway inflammation causing airway remodeling. However these lesions are all potentially reversible and there is little radiological evidence indicating lung destruction (pulmonary emphysema), which is potentially irreversible, in non-smoking asthmatics. Severe chronic respiratory failure is the major cause of mortality in patients with severe chronic lung diseases. Domiciliary long-term oxygen therapy (LTOT) is an accepted treatment for patients with severe chronic respiratory failure. Our reasoning, therefore, was that if asthma is a cause of severe chronic respiratory failure in non-smokers we should be able to find non-smoking asthmatics within a large population of patients on LTOT. The aim of our study (Asthma and Long-term Oxygen Therapy, "ALOT") was to investigate the prevalence of non-smoking asthmatics in patients on LTOT in a multi-centre, cross-sectional study. METHODS: Between June and September 2003 we screened all subjects on long-term domiciliary oxygen therapy in three different hospitals in the North-East area of Italy (within the provinces of Ferrara and Bologna). Taken collectively, we have found one-hundred and eighty-four patients on LTOT. We have reviewed their clinical data (age, sex, smoking, history and physical examination, arterial blood gas analysis, pulmonary function). RESULTS: 114 patients (all smokers) fulfilled the diagnostic criteria for COPD. Seventy patients (all smokers) had other diseases. We were unable to find any non-smokers in our screened population of subjects on long-term domiciliary oxygen therapy. Furthermore, there was no past history of asthma and/or acute wheezing episodes in either of the patient groups. CONCLUSIONS: This data suggests that asthma is an uncommon cause of severe chronic respiratory failure necessitating long-term domiciliary oxygen therapy in non-smokers and supports the current consensus that asthma and COPD are different diseases with differing stages of severity and the concept that long-term avoidance of active smoking is fundamental for the prevention of severe chronic respiratory failure.

Low-dose dexamethasone in the rat: a model to study insulin resistance.

The main aim of this study was to set up a new animal model to study insulin resistance. Wistar rats (6 or 7 per group) received the following for 4 wk in experiment 1: 1) vehicle, 2) 2 microg/day subcutaneous dexamethasone, 3) metformin (400 mg x kg(-1) x day(-1) os), and 4) dexamethasone plus metformin. In experiment 2 the rats received the following: 1) vehicle, 2) dexamethasone, 3) dexamethasone plus arginine (2%; as substrate of the nitric oxide synthase for nitric oxide production) in tap water, and 4) dexamethasone plus isosorbide dinitrate (70 mg/kg; as direct nitric oxide donor) in tap water. Insulin sensitivity was significantly reduced by dexamethasone already at week 1, before the increase in blood pressure (day 15) and without significant changes in body weight compared with vehicle. Dexamethasone-treated rats had significantly higher triglycerides, hematocrit, and insulin, whereas serum total nitrates/ nitrites were lower compared with vehicle. The concomitant treatment with metformin minimized all the described effects of dexamethasone. In experiment 2, only isosorbide dinitrate was able to prevent the observed dexamethasone-induced metabolic, hemodynamic, and insulin sensitivity changes. Chronic low-dose subcutaneous dexamethasone (2 microg/day) is a useful model to study the relationships between insulin resistance and blood pressure in the rat, and dexamethasone might decrease insulin sensitivity and increase blood pressure through an endothelium-mediated mechanism.

Autonomic nervous system activity and life threatening arrhythmias in experimental epilepsy.

In the present study the possible derangement of the autonomic system and its influence in life threatening arrhythmias were analysed during paroxysmal activity. In hemispherectomized rats a paroxysmal activation of the hypothalamic and mesencephalic cardioarrhythmogenic triggers was performed by topical application of penicillin-G. Blood gas parameters and electrical activity of the thalamus, hypothalamus, vagal nerve fibre, ECG and arterial blood pressure were simultaneously monitored in basal conditions and repeated after the appearance of paroxysmal activity. Temporal correlation analysis was carried out. Results showed that during activation of these triggers, the spontaneous vagal nerve fibre activity significantly increased and triggered the appearance of cardiac arrhythmias which could become life threatening and induce animal death when blood gas and electrolytic parameters were simultaneously impaired. These experiments suggest that fatal evolution of the heart impairment is related not only to an autonomic cardiac trigger, but also to a concomitant metabolic derangement, which most likely shares the same autonomic origin.

Ausentismo laboral en el personal médico Hospital Dr. Francisco Moscoso Puello / Work absence of the medical staff at the \"Francisco Moscoso Puello\" Hospital

Se realizó un estudio descriptivo con el objetivo de determinar la frecuencia y las causas del ausentismo laboral en 50 médicos escogidos al azar del Hospital Dr. Francisco M. Moscoso Puello durante el período enero-junio de 1996. Encontrándose que un 38// se ausentaban de su trabajo; el 52.6// los hicieron por enfermedad; las mujeres se ausentaron más que los hombres; el 89.5// de los ausentados no se encuentran satisfecho en la labor que desempeñan y el 57.9// señalaron que las condiciones de trabajo eran inadecuadas

Aspecific bronchial hyperreactivity in pulmonary sarcoidosis.

Aspecific bronchial hyperreactivity (A.B.H.) is a condition found mostly in cases of bronchial asthma, but it may also present in other pathologies affecting the respiratory tract. This study examines 30 patients presenting hilo-pulmonary sarcoidosis, 27 asthmatic patients and 25 healthy subjects as controls. The three groups were sex and age matched. No significant difference in smoking habits between controls and sarcoidosis patients was found. Patients were tested for aspecific bronchial hyperreactivity by administering increasing doses of methacholine. Methacholine inhalation was performed following a dosimetric method. Aspecific bronchial hyperreactivity was found in 6 (20.6%) of sarcoidosis patients with a significant frequency (p < 0.05). No statistically significant difference was found for mean PD20FEV1 values, but the difference between asthma and sarcoidosis patients was highly significant (p = 0.003). No statistically significant difference was found between basal FEV1 means expressed as a percentage of the former in asthmatics and sarcoidosis patients, both responsive and unresponsive. Although it is difficult to draw conclusions from these findings, aspecific bronchial hyperreactivity was seen to increase in subjects with sarcoidosis, and this may explain the not rare association between asthma and sarcoidosis.

[Mycoplasma pneumoniae pneumonia. Can radiologic features suggest the etiologic agent?]. / La polmonite da Mycoplasma pneumoniae. Gli aspetti radiologici possono indirizzare verso l'agente eziologico?

The present study was aimed at evaluating whether Mycoplasma pneumoniae (MP) pneumonia presents with typical X-ray patterns which can help its diagnosis. The chest films of 32 adult patients with serologically proven MP infections were reviewed. Confluent or patchy consolidation was the most common finding (66% of patients), interstitial involvement was much less frequent (19%), and so were "mixed" patterns (15%). Unilateral involvement was common (69%), the lower lobes were frequently involved (52%) and in 78% of cases only one lobe was affected. Pleural fluid (40%) and atelectasis (31%) were commonly seen, while hilar adenopathy was rare (9%). In substantial agreement with previous studies, no distinctive X-ray pattern of MP pneumonia was found and marked differences were seen to exist in its radiographic appearance. Despite these obstacles, some characteristic X-ray findings were suggestive of MP pneumonia: diffuse/localized interstitial involvement appeared to be the most helpful sign, in combination with clinical and epidemiologic data. On the contrary, patchy and acinar consolidations are slightly suggestive of MP etiology.

A discordância na interpretação dos testes ergométricos / Disagreement in the interpretation of ergometric tests

Quarenta e um pacientes foram submetidos ao teste de esforco e a cinecoronariografia. Os testes foram avaliados por tres observadores pertencentes a diferentes servicos. A discordancia na avaliacao nos testes atingiu a 68% quanto a presenca de isquemia miocardica e a 38% quanto a suficiencia do esforco realizado. A discordancia global nos relatorios foi de 71%. Houve concordancia com a conduta do experimentador em suspender o exercicio ao teste (92%). Em relacao aos testes "positivos" e "negativos" segundo a opiniao predominante entre os observadores, a discordancia foi de, respectivamente, 67% e 39%. Nos testes duvidosos e inconclusivos atingiu a 100%. Em relacao a morfologia do segmento ST no tracado de controle, morfologias normais e patologicas corresponderam a 55% e 84%, respectivamente, de discordancia na avaliacao do teste. Em relacao a morfologia do segmento ST, a frequencia-pico,as discordancias na interpretacao do teste atingiram a 28%, 64% e 75% nos casos com segmento ST respectivamente normal, ascendente e descendente ou horizontal. A sensibilidade e a especificidade dos observadores na deteccao da molestia coronaria atraves do TE variaram, respectivamente, entre 19 a 63%, e 60% a 94%; no entanto a "performance" e a eficacia dos mesmos foi semelhante (p > 0,05)

Caracterización y propiedades oncogénicas de un virus endógeno ARN de la línea BHK-21 (C-13) de hamster: I- exaltación de las propiedades oncogénicas del virus por irradiación del huésped, II- importancia experimental y práctica / Characterization and oncogenic properties of an endogenous virus RNA of line BHK-21 (C-13) of hamster: I- exaltation of the oncogenic properties of the virus by irradiation of the host, II- experimental and practical importance

En la primera parte del trabajo se demostró que la inoculación en el animal del virus oncogénico endógeno extraído de la línea BHK-21 (C-13) no induce a neoplasia. Como este comportamiento puede explicarse en función del grado de actividad oncogénica de la partícula se intentó comprobar esta hipótesis investigando la posibilidad de modificar el comportamiento del virus exaltando estas propiedades. Esta línea de investigación se fundamentó en los trabajos realizados mediante los cuales se demostró que la irradiación total del cuerpo del animal experimental exaltaba la virulencia de un picornavirus (aftosa). Se consideró además que este procedimiento aplicado a un virus oncogénico proporcionaría un modelo experimental interesante para la investigación del comportamiento de las propiedades oncogénicas virales modificando por radiaciones las condiciones del huésped... (TRUNCADO)(AU)

Caracterización y propiedades oncogénicas de un virus endógeno ARN de la línea BHK-21 (C-13) de hamster: I- exaltación de las propiedades oncogénicas del virus por irradiación del huésped, II- importancia experimental y práctica / Characterization and oncogenic properties of an endogenous virus RNA of line BHK-21 (C-13) of hamster: I- exaltation of the oncogenic properties of the virus by irradiation of the host, II- experimental and practical importance

En la primera parte del trabajo se demostró que la inoculación en el animal del virus oncogénico endógeno extraído de la línea BHK-21 (C-13) no induce a neoplasia. Como este comportamiento puede explicarse en función del grado de actividad oncogénica de la partícula se intentó comprobar esta hipótesis investigando la posibilidad de modificar el comportamiento del virus exaltando estas propiedades. Esta línea de investigación se fundamentó en los trabajos realizados mediante los cuales se demostró que la irradiación total del cuerpo del animal experimental exaltaba la virulencia de un picornavirus (aftosa). Se consideró además que este procedimiento aplicado a un virus oncogénico proporcionaría un modelo experimental interesante para la investigación del comportamiento de las propiedades oncogénicas virales modificando por radiaciones las condiciones del huésped... (TRUNCADO)