“Lo bueno dura poco”: disminuir las emociones positivas influye en nuestros niveles de optimismo

xxA pesar del creciente interés en la comprensión de las estrategias de regulación emocional (RE) de las emociones positivas y su relación con la salud mental, la relación entre los diferentes estilos de respuesta al afecto positivo y estilos cognitivos como el optimismo aún no se ha probado empíricamente. El objetivo del presente estudio fue evaluar el efecto de las estrategias para regular emociones positivas (evaluadas por el cuestionario Response to Positive Affect -RPA) sobre el optimismo, y la posible mediación del afecto positivo en esta relación. 250 participantes completaron el cuestionario RPA, medidas de optimismo y afecto positivo, y realizaron un procedimiento de inducción emocional aplicado a través de Internet. Los resultados muestran que el afecto positivo no media la relación entre las estrategias de regulación emocional y los niveles de optimismo. No obstante, disminuir las emociones positivas (“dampening”) fue la única estrategia que predijo los niveles de optimismo después de la inducción. Se señala la necesidad de nuevos estudios con el fin de mejorar la comprensión de los mecanismos implicados en la regulación y el optimismo.

Engaging in Awkward Social Interactions in a Virtual Environment Designed for Exposure-Based Psychotherapy for People with Generalized Social Anxiety Disorder: An International Multisite Study

The effectiveness of in virtuo exposure-based treatment of performance-only social anxiety disorder (SAD) has been demonstrated in several studies. However, few studies have validated virtual environments with participants suffering from generalized SAD. The goal of this study is to confirm the potential of a virtual environment in inducing anxiety in adults suffering from generalized SAD, compared to adults without SAD, when engaged in awkward social interactions. Differences between participants from two different countries were also explored. The sample consisted of 15 participants with SAD from Canada, 17 participants without SAD from Canada, 16 participants with SAD from Spain, and 21 participants without SAD from Spain. All participants were immersed in a control virtual environment and in an experimental virtual environment considered potentially anxiety-inducing for individuals with generalized SAD. As hypothesized, results showed that the experimental virtual environment induced a higher level of anxiety than the control environment among participants with SAD compared to those without SAD. The impact on anxiety of each socially threatening task performed during the experimental immersion was statistically significant. In terms of anxiety responses, no significant differences were found between participants from Canada and Spain. However, spatial presence and ecological validity were higher in Canadians than in Spaniards. Unwanted negative side effects induced by immersions in virtual reality were higher in the SAD group. This study highlights the importance for therapists to engage people with SAD in clinically relevant tasks while immersed in VR psychotherapeutic applications

Kisspeptin-mediated improvement of sensitivity to BRAF inhibitors in vemurafenib-resistant melanoma cells

Metastatic dissemination is still one of the major causes of death of melanoma’s patients. KiSS1 is a metastasis suppressor originally identified in melanoma cells, known to play an important physiological role in mammals’ development and puberty. It has been previously shown that expression of KiSS1 could be increased in lung cancer cells using epigenetic agents, and that KiSS1 could have a pro-apoptotic action in combination with cisplatin. Thus, the aim of the present study was to examine in human melanoma vemurafenib sensitive- and -resistant BRAF mutant cells characterized by different mutational profiles and KiSS1, KiSS1 receptor and KiSS1 drug-induced release, if peptides derived from KiSS1 cleavage, i.e., kisspeptin 54, could increase the sensitivity to vemurafenib of human melanoma, using cellular, molecular and biochemical approaches. We found that kisspeptin 54 increases vemurafenib pro-apoptotic activity in a statistically significant manner, also in drug resistant cellular models. The efficacy of the combination appears to reflect the intrinsic susceptibility of each cell line to PLX4032-induced apoptosis, together with the different mutational profile as well as perturbation of proteins regulating the apoptotic pathway, The results presented here highlight the possibility to exploit KiSS1 to modulate the apoptotic response to therapeutically relevant agents, suggesting a multitasking function of this metastasis suppressor

Teimoso como uma mula e mais carregado que burro de mascate: heranças linguístico-culturais em expressões idiomáticas de matriz comparativa

Estudar a fraseologia de uma determinada língua permite observar aspectos sociais e culturais da(s) comunidade(s) que a fala(m). Ao investigar o papel dos tropeiros na história do Brasil nos séculos XVIII e XIX, bem como sua contribuição para o acervo lexical da língua portuguesa, deparamo-nos com muitas expressões idiomáticas que refletem o modo de vida daqueles que cruzaram o país, do sul ao nordeste, transportando mercadorias para abastecer os mercados e levando muares para serem comercializados na grande feira de Sorocaba. Este trabalho volta-se para as expressões idiomáticas de matriz comparativa que incluem os zoônimos burro e mula em sua relação com o fenômeno do tropeirismo. Inicialmente, apresentamos algumas informações de cunho teórico a respeito de expressões idiomáticas, focalizando as de matriz comparativa. A seguir, apresentamos dados relevantes sobre o tropeirismo e o papel de burros e mulas nesse contexto. São então apresentadas e analisadas 16 expressões idiomáticas de matriz comparativa, coletadas em antologias e dicionários de fraseologia. Buscamos, por fim, evidenciar traços da herança linguístico-cultural deixada pelo tropeirismo em seus mais de dois séculos de atividade no Brasil

A computational multiscale strategy of the study of amorphous materials

A first step towards a computational Si–O–P angles, respectively. Other geometrical featuresmultiscale approach has been adopted here to deal with are in excellent agreement within the two approaches.the computational simulation of the Hench bioglass Electronic properties of the Hench bioglass have been45S5, an amorphous material of 48.1% SiO2 , 25.9% reported at B3LYP for the first time and both Mullik-CaO, 22.2% Na2 O and 3.7% P2 O5 composition. Molec- en charges and electronic band structure show a ratherular dynamics simulations based on classical force fields ionic character of the material, whereas a band gap offollowed by static minimizations on quenched structures about 6.5 eV characterizes the bioglass as a strong insu-have been run on a unit cell size suitable for subsequent lator. Work presently in progress will soon allow theab initio calculations. The molecular mechanics opti- information to be transferred from the B3LYP calcu-mized unit cell envisaging 78 atoms of Na12 Ca7 P2 Si13 lations to the molecular mechanics engine in order toO44 composition and P1 symmetry has then been fully refine the presently available empirical force fields foroptimized (both unit cell parameters and internal coor- complex ionic systems and their surfaces.dinates) at B3LYP level in a periodic approach usinggaussian basis sets of double-ζ quality and the devel-opment version of the CRYSTAL03 code. Comparisonbetween the molecular mechanics and B3LYP optimizedstructures shows the latter to give a slightly higherdensity than the former, due to overestimation of theSi–O bonds and underestimation of the Si–O–Si an

A brief guide to performing pharmacological studies in vitro: Reflections from the EORTC-PAMM Course “Preclinical and Early-phase Clinical Pharmacology”

One aim of cell-based in vitro assays is to identify the best drug candidate to develop using the best tumor cell model. This is challenging in every anticancer drug discovery process. Briefly, we summarize the parameters to be taken into account when performing in vitro cell assays, in order to obtain reliable and reproducible results, which was fundamentally discussed by lecturers at the educational course on preclinical and early-phase clinical pharmacology studies, at the 40th Winter Meeting of the Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer. Moreover, specific cellular sensitivity tests are described. In addition to monolayer in vitro cell models for the screening of new potential candidate drugs, three-dimensional tumor/cell tissue models are emerging as new pre-clinical tools that more closely reflect the in vivo microenvironment. Therefore, the use of different in vitro models for drug screening can enhance the predictability and reliability of preclinical drug-discovery phases and target validation

An ab initio parameterized interatomic force field for hydroxyapatite

A classical interatomic force field for hydroxyapatite has been parameterized from periodicab initio calculations carried out on the hexagonal structure (space group P63). The GULPprogram has been used for fitting geometry and phonon frequencies computed with theCRYSTAL06 program using the B3LYP hybrid functional and Gaussian-type basis set ofpolarized double zeta quality. Polarization effects and covalent bonding have been includedthrough the shell-ion model potential. Excellent agreement has been found in reproducingstructural features, lattice dynamics, the OH stretching vibrations and relative phase stabilitiesbetween the monoclinic structure (space group P21/b) and the hexagonal one. Transferability fromhydroxyapatite to other calcium phosphates has also been demonstrated

FFSiOH: a New Force Field for Silica Polymorphs and Their Hydroxylated Surfaces Based on Periodic B3LYP Calculations

A partial charge shell-ion model potential for silica polymorphs and their hydroxylated surfaces(FFSiOH) was parametrized in a self-consistent way using periodic B3LYP results for bulk R-cristobaliteand the (100) and (001) hydroxylated surfaces. The reliability of the new potentials was checked bycomparing structures, vibrational frequencies and relative phase stabilities of dense bulk silica polymorphs,namely R-quartz, R-cristobalite, R-tridymite, and Stishovite with both experimental and B3LYP data.The FFSiOH was also checked for computing structural and vibrational features of representative all-silica microporous materials, namely edingtonite, chabazite, and faujasite. As a last step, FFSiOH wasadopted to predict OH stretching vibrational frequencies and relative thermodynamic stability of themost common fully hydroxylated surfaces of the dense silica polymorphs, the (100) and (001) facesof all-silica edingtonite, the features of the local Si-defect in chabazite and sodalite known as (SiOH)4hydrogarnet and the geometries of H-bonded silanol groups of an amorphous silica surface. In all casesexcellent agreement resulted between FFSiOH and B3LYP periodic data and experimental data, whenavailable. The new FFSiOH force field opens up the molecular simulation of materials in which thesurface hydroxyl groups play a key role, as is the case for amorphous silica surfaces, all-silica zeoliteexternal surfaces, and the internal walls of mesoporous materials

Efficacy of a Selective Binder of α_Vβ₃ Integrin Linked to the Tyrosine Kinase Inhibitor Sunitinib in Ovarian Carcinoma Preclinical Models

Ovarian carcinoma, the most lethal gynecological cancer, is characterized by late diagnosis, with drug resistance limiting the efficacy of platinum-based therapy. Since some integrins are upregulated in cancer, including ovarian carcinoma, they represent a potential target for drug delivery. Receptor tyrosine kinases are also deregulated in cancer and their expression has been associated with drug resistance. Here, the antitumor effects of three conjugates possessing a selective binder of the extracellular portion of integrin αVβ3 covalently linked to the tyrosine kinase inhibitor sunitinib were investigated in cisplatin-sensitive and -resistant ovarian carcinoma cells expressing both tyrosine kinase VEGFR2 and αVβ3 at different levels. We found that one of the three compounds was active in inhibiting the growth of both drug-sensitive and -resistant cells in the micromolar range with a slightly increased potency in resistant cells as compared to sunitinib. The same compound markedly impaired cell migratory and invasive abilities and reduced paxillin phosphorylation. Antitumor activity studies in IGROV-1/Pt1 cells xenografted in nude mice revealed a striking activity of this conjugate versus sunitinib. Taken together, our results support the interest of integrin-targeted sunitinib conjugates for the treatment of drug-resistant tumors