Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotypic spectrum underlying tetrahydrobiopterin metabolism defects: Experience in a single Mexican reference center.

Background: Pterin profiles or molecular analyses of hyperphenylalaninemia (HPA) caused by phenylalanine hydroxylase (PAH) deficiency or tetrahydrobiopterin deficiency (BH4D) are not always available in low- or middle-income countries, including Mexico, limiting information regarding the phenotypic and genotypic characteristics of patients exhibiting BH4D. Objective: To report the genotypes underlying BH4D and the clinical presentation in unrelated Mexican HPA pediatric patients with normal PAH genotypes who attended a single metabolic reference center in Mexico. Methods: Automated Sanger sequencing of the PTS, QDPR, and PCBD1 genes of 14 HPA patients was performed. Predicted effects on protein structure caused by missense variants were assessed by in silico protein modeling. Results and discussion: A high prevalence of BH4D was noted in our HPA cohort (9.8%, N = 14/142). Clinically relevant biallelic genotypes were identified in the PTS (N = 7/14 patients), QDPR (N = 6/14 patients), and PCBD1 (N = 1/14 patients) genes. Four novel QDPR variants [c.714dup or p.(Leu239Thrfs*44), c.106-1G>T or p.(?), c.214G>T or p.(Gly72*), and c.187_189dup or p.(Gln63dup)] were identified. In silico protein modeling of six missense variants of PTS [p.(Thr67Met), p.(Glu81Ala), and p.(Tyr113Cys)], QDPR [p.(Cys161Phe) and p.(Pro172Leu)], and PCBD1 [p.(Glu97Lys)] supports their pathogenicity. Progressive neurological symptoms (mainly intellectual and motor impairment and even death in three patients) were noted in all patients with biallelic QDPR genotypes and in 5/7 patients bearing biallelic PTS genotypes. The single homozygous PCBD1 p.(Glu97Lys) patient remains asymptomatic. Conclusion: A higher proportion of BH4D (9.8 vs. 1%-2% worldwide), attributable to a heterogeneous mutational spectrum and wide clinical presentation, was noted in our Mexican HPA cohort, with the PTS-related HPA disorder being the most frequent. Sequencing-based assays could be a reliable approach for diagnosing BH4D in our population.

Photonics bridges between turbulence and spin glass phenomena in the 2021 Nobel Prize in Physics.

A photonic connection between turbulence and spin glasses has been recently established both theoretically and experimentally using a random fiber laser as a photonic platform. Besides unveiling this interplay, it links the works of two 2021 Nobel laureates in Physics.

Hemorragia del tracto digestivo superior, enfoque para el médico general / Upper digestive tract bleeding, approach for the general Practitioner / Hemorragia do trato digestivo superior, enfoque para o médico geral

La hemorragia del tracto digestivo superior (HTDS) es el sangrado originado por encima del ángulo de Treitz. A pesar del aumento en las estrategias de prevención, del incremento en los tratamientos con Inhibidor de bomba de protones (IBP) y de la intervención endoscópica temprana, esta patología sigue siendo una causa frecuente de consulta a urgencias, con una morbimortalidad no despreciable y alta carga para el sistema de salud. Esta revisión se enfoca en la HTDS de causa diferente a las varices. La principal causante de esta entidad es la enfermedad ácido-péptica, que es consecuencia del gran consumo de antiinflamatorios no esteroideos (AINES) y de la infección por Helicobacter Pylori. Otras causas son el síndrome de Mallory Weiss, la esofagitis erosiva, las malformaciones arteriovenosas y la malignidad.

Upper gastrointestinal bleeding (UGIB) refers to any bleeding originating above the angle of Treitz. Despite an increase in prevention strategies, proton pump inhibitor (PPI) therapy and early endoscopic intervention, this pathology continues to be an important cause of admission to the emergency department for gastrointestinal causes, having a pretty high morbidity and mortality in addition to a high burden on the health system. This review focuses on non-variceal UGIB. The main cause of this entity being peptic acid disease, due to great consumption of NSAIDs and Helicobacter Pylori infection. Other causes are Mallory Weiss syndrome, erosive esophagitis, arteriovenous malformations, and malignancy.

A hemorragia do trato digestivo superior (HTDS) é o sangrado originado acima do ângulo de Treitz. Apesar do aumento nas estratégias de prevenção, do incremento nos tratamentos com Inibidor da bomba de prótons (IBP) e da intervenção endoscópica precoce, esta patologia segue sendo uma causa frequente de consulta a urgências, com uma morbimortalidade não depreciável e alta carga para o sistema de saúde. Esta revisão se enfoca na HTDS de causa diferente às varizes. A principal causante desta entidade é a doença ácido-péptica, que é consequência do grande consumo de anti-inflamatórios não esteróideos (AINES) e da infecção por HelicobacterPylori. Outras causas são a síndrome de Mallory Weiss, a esofagites erosiva, as malformações arteriovenosas e a malignidade. Palavras-chave: hemorragia gastrointestinal; úlcera péptica; endoscopia gastrointestinal; inibidores da bomba de prótons; medicina geral.

[Evaluation of diaphragmatic paralysis with ultrasound and spirometry: comparison of supraclavicular vs interscalene block in shoulder surgery]. / Evaluación de la parálisis diafragmática con ultrasonido y espirometría: comparación del bloqueo supraclavicular vs bloqueo interescalénico en cirugía de hombro.

INTRODUCTION: arthroscopic shoulder surgery has recently gained popularity, however, postoperative pain is reported as moderate to severe. Regional anesthesia is useful for the control of postoperative pain. Interscalene and supraclavicular blocks produce diaphragmatic paralysis in different proportions. The aim of this study is to find the percentage and duration of hemidiaphragmatic paralysis, by means of ultrasonographic measurements, correlated with spirometry, comparing the supraclavicular approach with interscalene. MATERIAL AND METHODS: clinical, controlled and randomized trial. Fifty-two patients, between 18 and 90 years of age, scheduled for arthroscopic shoulder surgery were included, divided into 2 groups (interscalene or supraclavicular block). Diaphragmatic excursion was measured and spirometry was performed prior to admission to the operating room and 24 hours after installation of the block, the study concluded 24 hours after the anesthetic event. RESULTS: vital capacity was reduced by 0.7% in the supraclavicular block and 7.7% for the interscalene, FEV1 was reduced by 0.2% for the supraclavicular and 9.5% in the interscalene with a statistically significant difference (p = 0.001). Diaphragmatic paralysis in spontaneous ventilation appeared in both approaches at 30 minutes, without significant difference. At 6 and 8 hours, paralysis continued in the interscalene group, while in the supraclavicular approach it remained preserved compared to the baseline. CONCLUSIONS: supraclavicular block is as effective as interscalene block in arthroscopic shoulder surgery, with less diaphragmatic block (1.5 times more diaphragmatic paralysis in interscalene).

INTRODUCCIÓN: la cirugía artroscópica de hombro ha ganado popularidad recientemente; sin embargo, el dolor postquirúrgico se reporta de moderado a severo. La anestesia regional es útil para el control del dolor postquirúrgico. El bloqueo interescalénico y supraclavicular produce parálisis diafragmática en diferente proporción. Se busca encontrar cuál es el porcentaje y duración de la parálisis hemidiafragmática mediante mediciones ultrasonográficas, correlacionadas con espirometría comparando el abordaje supraclavicular con interescalénico. MATERIAL Y MÉTODOS: ensayo clínico, controlado y aleatorizado. Se incluyeron 52 pacientes entre 18 y 90 años, programados para cirugía artroscópica de hombro, divididos en dos grupos (bloqueo interescalénico y supraclavicular). Se midió la excursión diafragmática y se realizó una espirometría previo al ingreso al quirófano y a las 24 horas de instalación del bloqueo, el estudio concluyó a las 24 horas del evento anestésico. RESULTADOS: la capacidad vital se redujo en 0.7% en el grupo del bloqueo supraclavicular y 7.7% en el grupo interescalénico, el VEF1 se redujo en 0.2% en el supraclavicular y 9.5% en el interescalénico con una diferencia estadísticamente significativa (p = 0.001). La parálisis diafragmática en ventilación espontánea se presentó en ambos abordajes a los 30 minutos, sin diferencia significativa. A las seis y ocho horas continuó la parálisis en el grupo interescalénico, mientras que en el abordaje supraclavicular se mantuvo en comparación con la basal. CONCLUSIONES: el bloqueo supraclavicular resulta tan efectivo como el bloqueo interescalénico en la cirugía artroscópica de hombro, con menor bloqueo diafragmático (1.5 veces más parálisis diafragmática en el interescalénico).

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse.

The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Safety and efficacy of urethroplasty based on age groups.

OBJECTIVE: To analyze the results and complications after urethroplasty based on patient age groups. As secondary objective, we analyzed the impact of operative complexity on each age group. MATERIAL AND METHODS: This is a retrospective cohort study that include male patients who underwent urethroplasty between January 2011 and December 2018. Data was obtained from the patients' electronic health records. Patients were grouped as follows: <60 years, 60-79 years and >80 years. Variables evaluated were history, comorbidities, previous surgeries and operative complexity. Restenosis-free survival and complications presented in each group were determined according to the Clavien-Dindo classification system. The SPSS® program was used for statistical analysis. RESULTS: A total of 783 patients were included, and the mean follow-up was 19 months. The estimated 2-year restenosis-free survival in the population under 60, 60-79 and over 80 years was 87, 87 and 93.9% (IC 95%), respectively. Univariate analysis showed that the age group was not a predictor of restenosis. Complex surgery is the only predictor of recurrence, increasing the risk by 60% (HR 1.64, 95% CI 1.05-2.56, p = 0.029). There was an overall complication rate of 30.8%, and 62% of these were Clavien ≤ II. We found no association between the frequency of complications and age. CONCLUSIONS: Urethroplasty is safe and effective regardless of age group. There are no statistically significant differences in outcomes and complications shown by the age group comparison. There were no significant differences when analyzing the impact of complex surgeries among the different age groups. The data indicate that age alone should not be taken as an absolute exclusion criterion for patients needing urethral reconstruction.

Dicke and Fano-Andreev reflections in a triple quantum-dot system.

This article studies quantum interference effects and their influence on the electronic transport through a parallel triple quantum-dot system coupled to normal and superconducting leads in the linear response and non-equilibrium regime. We model the system by a triple impurity Anderson Hamiltonian including the Coulomb intra-dot correlations in all quantum-dots. Using the non-equilibrium Green's function formalism, we calculate the Andreev conductance and the transmittance for energies within the superconductor gap. Our results show that the Andreev reflection spectra, both in the presence and absence of Coulomb interaction, reveal Fano and Dicke-like resonances in analogy to the Fano and Dicke effects in atomic physics. As one of the main results, we obtain that the charge shows abrupt changes due to the Dicke effect.

Abnormalities in subsets of B and T cells in Mexican patients with inborn errors of propionate metabolism: observations from a single-center case series.

BACKGROUND: Propionate inborn errors of metabolism (PIEM), including propionic (PA) and methylmalonic (MMA) acidemias, are inherited metabolic diseases characterized by toxic accumulation of propionic, 3-hydroxypropionic, methylcitric, and methylmalonic organic acids in biological fluids, causing recurrent acute metabolic acidosis events and encephalopathy, which can lead to fatal outcomes if managed inadequately. PIEM patients can develop hematological abnormalities and immunodeficiency, either as part of the initial clinical presentation or as chronic complications. The origin and characteristics of these abnormalities have been studied poorly. Thus, the aim of the present work was to evaluate and describe lymphoid, myeloid, and erythroid cell population profiles in a group of clinically stable PIEM patients. METHODS: This was a retrospective study of 11 nonrelated Mexican PIEM patients. Clinical, biochemical, nutritional, hematological, and lymphocyte subsets were analyzed. RESULTS: Despite being considered clinically stable, 91% of patients had hematological or immunological abnormalities. The absolute lymphocyte subset counts were low in all patients but one, with CD4+ T-cell lymphopenia, being the most common one. Furthermore, of the 11 studied subjects, nine presented with a low CD4/CD8 ratio. Among the observed hematological alterations, bicytopenia was the most common (82%) one, followed by anemia (27%). CONCLUSION: Our results contribute to the landscape of immunological abnormalities observed previously in PIEM patients; these abnormalities can become a life-threatening chronic complications because of the increased risk of opportunistic diseases. These findings allow us to propose the inclusion of monitoring immune biomarkers, such as subsets of lymphocytes in the follow up of PIEM patients.

Trimethylamine N-oxide levels are associated with NASH in obese subjects with type 2 diabetes.

AIMS: Trimethylamine N-oxide (TMAO), choline and betaine serum levels have been associated with metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). These associations could be mediated by insulin resistance. However, the relationships among these metabolites, insulin resistance and NAFLD have not been thoroughly investigated. Moreover, it has recently been suggested that TMAO could play a role in NAFLD by altering bile acid metabolism. We examined the association between circulating TMAO, choline and betaine levels and NAFLD in obese subjects. METHODS: Serum TMAO, choline, betaine and bile acid levels were measured in 357 Mexican obese patients with different grades of NAFLD as determined by liver histology. Associations of NAFLD with TMAO, choline and betaine levels were tested. Moreover, association of TMAO levels with non-alcoholic steatohepatitis (NASH) was tested separately in patients with and without T2D. RESULTS: TMAO and choline levels were significantly associated with NAFLD histologic features and NASH risk. While increased serum TMAO levels were significantly associated with NASH in patients with T2D, in non-T2D subjects this association lost significance after adjusting for sex, BMI and HOMA2-IR. Moreover, circulating secondary bile acids were associated both with increased TMAO levels and NASH. CONCLUSIONS: In obese patients, circulating TMAO levels were associated with NASH mainly in the presence of T2D. Functional studies are required to evaluate the role of insulin resistance and T2D in this association, both highly prevalent in NASH patients.

Colloidal and polymeric contributions to the yielding of dense microgel suspensions.

HYPOTHESIS: Soft microgel colloids can be densely packed since particle networks can compress and interpenetrate. This evolution of the particle's internal structure associated with packing is expected to determine the linear viscoelastic properties and the yielding behavior of dense suspensions of microgel colloids. EXPERIMENTS: We investigated the volume fraction-dependent linear and non-linear rheological response of suspensions of soft core-shell particles formed by a poly(N-isopropylacrylamide) (PNIPAM) microgel core and a thin poly(ethylene glycol) (PEG) shell. FINDINGS: The linear viscoelasticity of suspensions reveals a transition from a fluid to a jammed glass state. Increasing volume fraction within the jammed state, the linear storage modulus and the yield stress show distinct regimes associated with the evolution of particle contacts, which involve progressive compression and interpenetration of the shell and core. The yielding of jammed suspensions occurs in two-steps: At small strains jammed cages are rearranged, while full disentanglement of interpenetrating networks only occurs at large deformations and results in fluidization. Yield strains and stresses increase with increasing shear rate or frequency, suggesting a progressive dominance of the timescale associated with shear over that associated with the internal dynamics of the system.

Evaluation of highly sensitive diagnostic tools for the detection of P. falciparum in pregnant women attending antenatal care visits in Colombia.

BACKGROUND: In low transmission settings early diagnosis is the main strategy to reduce adverse outcomes of malaria in pregnancy; however, microscopy and rapid diagnostic tests (RDTs) are inadequate for detecting low-density infections. We studied the performance of the highly sensitive-RDT (hsRDT) and the loop mediated isothermal DNA amplification (LAMP) for the detection of P. falciparum in pregnant women. METHODS: A cross-sectional study was conducted in two malaria-endemic municipalities in Colombia. We screened pregnant women in the context of an antenatal care program in health facilities and evaluated five tests (microscopy, conventional RDT, hsRDT, LAMP and nested polymerase chain reaction-PCR) for the detection of P. falciparum in peripheral blood, using a quantitative reverse transcription PCR (qRT-PCR) as the reference standard. Diagnostic performance of hsRDT and LAMP were compared with routine testing. RESULTS: The prevalence of P. falciparum was 4.5% by qRT-PCR, half of those infections were subpatent. The sensitivity of the hsRDT (64.1%) was slightly better compared to microscopy and cRDT (59 and 53.8% respectively). LAMP had the highest sensitivity (89.7%) for detecting P. falciparum and the ability to detect very low-density infections (minimum parasite density detected 0.08 p/µL). CONCLUSIONS: There is an underestimation of Plasmodium spp. infections by tests routinely used in pregnant women attending antenatal care visits. LAMP methodology can be successfully implemented at local hospitals in malaria-endemic areas. The relevance of detecting and treating this sub-patent P. falciparum infections in pregnant women should be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172221 , Date of registration: May 29, 2017.

Safety and efficacy of urethroplasty based on age groups. / Seguridad y eficacia de la uretroplastia según grupos etarios.

OBJECTIVE: To analyze the results and complications after urethroplasty based on patient age groups. As secondary objective, we analyzed the impact of operative complexity on each age group. MATERIAL AND METHODS: This is a retrospective cohort study that include male patients who underwent urethroplasty between January 2011 and December 2018. Data was obtained from the patients' electronic health records. Patients were grouped as follows: < 60 years, 60-79 years and > 80 years. Variables evaluated were history, comorbidities, previous surgeries and operative complexity. Restenosis-free survival and complications presented in each group were determined according to the Clavien-Dindo classification system. The SPSS® program was used for statistical analysis. RESULTS: A total of 783 patients were included, and the mean follow-up was 19 months. The estimated 2-year restenosis-free survival in the population under 60, 60-79 and over 80 years was 87, 87 and 93.9% (IC 95%), respectively. Univariate analysis showed that the age group was not a predictor of restenosis. Complex surgery is the only predictor of recurrence, increasing the risk by 60% (HR 1.64, 95% CI 1.05-2.56, p = 0.029). There was an overall complication rate of 30.8%, and 62% of these were Clavien ≤ II. We found no association between the frequency of complications and age. CONCLUSIONS: Urethroplasty is safe and effective regardless of age group. There are no statistically significant differences in outcomes and complications shown by the age group comparison. There were no significant differences when analyzing the impact of complex surgeries among the different age groups. The data indicate that age alone should not be taken as an absolute exclusion criterion for patients needing urethral reconstruction.

RID: Evaluation of the Possible Inhibiting Effect of the Proinflammatory Signaling Induced by TNF-α through NF-κß and AP-1 in Two Cell Lines of Breast Cancer.

Receptor internalization and degradation (RID), is a transmembrane protein coded within the E3 region expression cassette of adenoviruses. RID downregulates the cell surface expression of epidermal growth factor receptor (EGFR), tumor necrosis factor receptor (TNFR), and apoptosis antigen 1 (FAS), causing a reduction of the effects of their respective ligands. In addition, RID inhibits apoptosis by decreasing the secretion of TNF-related apoptosis-inducing ligand (TRAIL) by normal tissue cells. In this article, we report that RID inhibited chemokine expression in human breast cancer cell line MDA-MB-231 but showed no effect in cell line MCF7. These dissimilar results may be due to the different molecular and functional properties of both cell lines. Therefore, it is necessary to replicate this study in other breast cancer cell models.

Unraveling the effects on lithium-ion cathode performance by cation doping M-Li2CuO2 solid solution samples (M = Mn, Fe and Ni).

Cation doping is one of the most dynamic strategies to enhance the electrochemical properties of cathode materials for lithium-ion batteries. Nevertheless, the maximum partial substitution capacity depends on the solubility of each metal ion, and so the formation of impurities is a very common consequence. Thus, the correlation between electrochemical performance and the doping effect is frequently unknown. In this study, the effect of the partial substitution of copper by manganese, iron or nickel in Li2CuO2 is evaluated, as well as the effect on the electrochemical performance of the modified Li2CuO2 samples as lithium ion battery cathode materials. XRD characterization confirmed single phase formation for all samples, and the incorporation of the transition metal in the Li2CuO2 structure was evaluated by XRD profile fitting, EPR and 7Li-NMR. The results showed modifications in intra- and inter-chain interactions, associated with the variations in the Cu-O-Cu bond angle and changes in magnetic order, due to the presence of the doping transition metal. Among all samples, only manganese partial substitution reveals a drastic improvement in the electrochemical stability during the charge/discharge processes even at potentials higher than 3.9 V. It was corroborated that the higher stability is attributed to (i) the increase in the superexchange interactions between the copper sites and manganese, directly modifying lithium diffusivity and electronic conductivity, both inferred from dynamic thermogravimetric analysis for CO2 sorption and conductivity tests, respectively and (ii) the lower propensity to enable O2 evolution during several charge cycles. These results are totally attributed to manganese cation partial substitution, which has a huge impact on the utilization of copper-based materials in real applications.

Centro de Isótopos: acciones en beneficio de la salud pública / Center of Isotope: actions for the benefit of public health

RESUMEN En tributo a los cinco siglos de ciudad el Centro de Isótopos hace recuento de su actividad. La obtención de compuestos marcados con radionucleidos y otros trabajos radioquímicos en el Instituto de Física Nuclear, inaugurado en 1969, estimularon las aplicaciones de las fuentes radiactivas abiertas, por lo que puede considerarse el antecedente organizado más palpable del centro. Posteriormente en los años 80, la Secretaria Ejecutiva para Asuntos Nucleares aceleró, diversificó y amplió las aplicaciones, desarrolló la formación de cuadros y especialistas y la colaboración internacional. La puesta en operación del Centro de Estudios Aplicados al Desarrollo de la Energía Nuclear coincidió con la consolidación de un grupo de instituciones de investigación y producción biotecnológica y con el auge de las aplicaciones en Medicina Nuclear. Pronto se reconoció que no era posible continuar el manejo de un inventario cada vez mayor de radionucleidos, por lo que se diseñó y construyó un centro especializado a ciclo completo: investigación-desarrollo, producción y comercialización, el CENTIS. Durante su integración en 1994 a la Agencia de Energía Nuclear, se concluyó la inversión y se establecieron las metodologías de producción de los más importantes radiofármacos. En más de 20 años de labor CENTIS se ha convertido en el principal soporte de la Medicina Nuclear del país. Con sus capacidades metrológicas en la magnitud radiactividad y sus investigaciones no clínicas y clínicas, se inserta de forma cada vez más estrecha en la vida socio-económica del país y su capital. En el trabajo se detallan los principales resultados de cada etapa en lo relacionado a la misión del centro y se hace una valoración técnica de hacia dónde se encaminan acciones en favor de sus sectores destino: salud e investigación biomédica. Lustros en favor de siglos.

ABSTRACT To commemorate the 500th anniversary of the city of Havana, the Isotope Center reviews its activity since its creation. The production of radionuclidemarked compounds and other radiochemical work at the Institute of Nuclear Physics, inaugurated in 1969, stimulated the applications of open radioactive sources, which can be considered as the most tangible organized antecedent of the center. Later in the 1980s, the Executive Secretary for Nuclear Affairs accelerated, diversified and expanded nuclear applications, developed the training of highly qualified staff and experts as well as international cooperation. The creation of the Center for Applied Nuclear Development Studies coincided with the consolidation of a group of biotechnological research and production institutions and with these applications gaining importance in Nuclear Medicine. It was soon recognized that it was not possible to continue managing a growing inventory of radionuclides. As a result, CENTIS, a specialized center with a complete cycle, was designed and built, which comprised not only research and development, but also production and marketing. When in 1994 CENTIS became part of the Nuclear Energy Agency, investment was concluded and the production methodologies of the most important radiopharmaceuticals were established. In more than 20 years of work CENTIS has become the main support of Nuclear Medicine in the country. With its metrological capabilities in the magnitude of radioactivity and its non-clinical and clinical research, it is increasingly part of the socio-economic life of the country and its capital. In this paper the main results of each stage are detailed in relation to the mission of the center and a technical assessment is made regarding the actions taken to favor their target sectors: health and biomedical research. Periods of five years in favor of centuries.

Confinement effect on the low temperature specific heat for ultrathin silicon nanowires: a first principles study.

This work studied the phonon confinement effects at the low temperature specific heat of Si nanowires from first principles using density functional perturbation theory. The nanowires were modeled in the [0 0 1] direction for three different diameters, with the largest cross section being approximately 10 Å. The results indicate the specific heat can be described at low temperatures using a third-grade polynomial of the form c v = λT + ßT 2 + γT3, where the coefficients of quadratic and cubic terms are almost nonexistent for small diameters. These terms begin to have relevance at larger diameters. Further analysis shows λ > ß > γ, which shows the phonon confinement (λ) and surface atoms (ß) become more important than the volumetric contribution (γ) for ultrathin nanowires at low temperatures.