Ambiente y TLC: el pacto de gobernabilidad

This paper aims at providing, from a sustainable development perspective, an idea about the direction our country will take once the US-Peru FTA is enforced, regarding particularly the environmental, trade and investment areas. The signing of the FTA has led Peru to leave behind a view of the environment vision as a moral and ethical (some times marginal) component of economic relations, to turn it into a regulatory and mandatory consideration overlapping trade and investment to such an extent that failure to comply may lead to sanctions as severe as those pertaining to other matters related to for instance access to or permanence in a given market. Even so, it is worthwhile mentioning that the FTA is only an initial component of a more complex and broad multilateral scenario that recognizes in the environment an essential element of international economic relations.El presente artículo pretende brindar, desde la perspectiva del desarrollo sostenible, una idea acerca de la dirección que tomará nuestro país a partir de la entrada en vigencia del TLC con Estados Uni-dos, en particular en lo referido a la relación entre lo ambiental y el comercio y la inversión. Nuestro propósito es que el lector aprecie que con la fi rma del TLC nuestro país ha transcendido la visión de lo ambiental como un componente moral o ético (y a veces marginal) de las relaciones económicas, para situarlo como un componente regulatorio y obligacional imbricado en el comercio y la inver-sión, a un punto tal que su incumplimiento puede acarrear sanciones tan severas como en cualquier otra materia relativa al acceso a mercados o su permanencia en ellos. Aun así, es menester aclarar que el TLC es apenas una expresión todavía inicial de un escenario multilateral más complejo y amplio, que reconoce en lo ambiental un elemento esencial de las relaciones económicas internacionales

La paradoja de la integración latinoamericana

Since its inception, Latin America has been, through its most illustrious thinkers, a focus of the regional integration in the world. Even though the ideas which, eventually, would inspire other thinkers elsewhere in the world to undertake their own integration projects are widely accepted and supported in the region, attempt after attempt for a Latin American integration has failed, either because of intrinsic or extrinsic motives, under its control or otherwise. The author, through a historical and economic analysis of the different Latin American integrationist initiatives tries to find the common denominator which has prevented the majority —if not all— of those projects from achieving their objective: a united America. She also studies the distinction and —apparent— conflict between supranationalism and intergovernmentalism, and how both models have led the projects which applied them to success or failure. The author concludes that it is a combination of factors, including the subscription of free trade agreements which, rather than integrating the region, isolate their signatories one from another; the regional idiosyncrasy and its nationalist aspirations which come and go; and the initiatives themselves which have gradually entangled its members, since they force them to decide whether to follow the directives of one or the other, which until now have impeded the real integration of the Latin American countries.Desde sus albores, la región latinoamericana ha sido, a través de sus pensadores más insignes, un foco de la integración regional en el mundo. Si bien las ideas que eventualmente inspirarían a otros pensadores en otras partes del globo a emprender sus propios procesos integracionistas son hasta ahora mayoritariamente aceptadas y apoyadas en la región, intento tras intento de integración latinoamericana ha fallado, sea por motivos intrínsecos o extrínsecos, bajo su control o no. La autora, mediante un análisis histórico y económico de las distintas iniciativas integracionistas latinoamericanas, intenta encontrar el común denominador que ha impedido a la mayoría —sino todos— de aquellos proyectos conseguir su objetivo: una América unida. Estudia además la distinción y —aparente— conflicto entre la supranacionalidad e intergubernamentalidad, y cómo ambos modelos han llevado a los proyectos que los aplicaron al éxito o al fracaso. La autora concluye que es una combinación de factores, entre la suscripción de acuerdos de libre comercio que, más que integrar a la región, aíslan a sus suscriptores uno del otro; la propia idiosincrasia regional y sus aspiraciones nacionalistas que van y vienen; y las mismas iniciativas que paulatinamente han ido enredando a sus miembros, pues los obligan a colocarse en la disyuntiva de seguir los lineamientos de una u otra, los que hasta ahora han prevenido la integración real de los países latinoamericanos

Eficácia do programa metacognitivo de intervenção na compreensão de leitura em estudantes do terceiro ano

This study examined the efficacy of a metacognitive intervention programme in a classroom group of 33 third-grade students. Two groups were formed: the intervention group with students in the classroom who showed reading delay and cognitive attention processes (n=8) and the comparison group (n=25). In the intervention group, a planning facilitation programme was implemented that aimed to improve inhibition processes and, correspondingly, overall reading comprehension indices. The Das-Naglieri: Cognitive Assessment System (D.N: CAS; Naglieri & Das, 1997) was used to measure attention processes. For reading processes, the Catalan et al. (2010) Reading Comprehension Assessment (ACL) test was used. The measurements were taken at pre-test, post-test, and follow-up. The results showed that the intervention group equalled the comparison group in reading comprehension and significantly improved in inhibition processes in the post and follow-up measures. It is concluded that the programme has had an impact on improving inhibition processes when facing reading activities.Este estudo analisou a eficácia do programa de intervenção metacognitiva numa turma de 33 alunos do terceiro ano. Foram formados dois grupos: o grupo de intervenção, com estudantes na sala de aula que demonstraram um atraso na leitura e nos processos de atenção cognitiva (n=8), e o grupo de comparação (n=25). No grupo de intervenção, um programa facilitador do planeamento foi implementado, visando melhorar os processos de inibição e, correspondentemente, os índices de leitura e compreensão de um modo geral. O Das-Naglieri: Cognitive Assessment System (D.N: CAS; Naglieri & Das, 1997) foi utilizado para medir os processos de atenção. Para os processos de leitura, o teste de Reading Comprehension Assessment (ACL) de Catalan et al. (2010) foi utilizado. As análises foram consideradas no pré-teste, pós-teste e follow-up. Os resultados demonstraram que a intervenção de grupo igualou o grupo de comparação na compreensão da leitura e melhorou significativamente nos processos de inibição nas análises do pós-teste e do acompanhamento. Conclui-se que o programa teve impacto na melhoraria dos processos de inibição quando consideradas as atividades de leitura

Inactivation of human plasma alters the structure and biomechanical properties of engineered tissues

Acknowledgments The authors are grateful to Echevarne Laboratories for the coagulation experiments and to Gloria Carmona and Rosario Sánchez Pernaute as well as all members of the Unidad de Producción y Reprogramación Celular (UPRC) for technical help and support. All figures were created through BioRender.com accessed on 1 September 2021.Funding This research was funded by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+i) from Ministerio de Ciencia, Innovación y Universidades (Instituto de Salud Carlos III), grants FIS PI17/0391, RTC-2017- 6658-1, PI20/0317 and ICI19/00024 (BIOCLEFT), co-financed by Fondo Europeo de Desarrollo Regional ERDF-FEDER, European Union and PE-0395-2019 from Consejería de Salud y Familias, Junta de Andalucía, Spain.Fibrin is widely used for tissue engineering applications. The use of blood derivatives, however, carries a high risk of transmission of infectious agents, necessitating the application of pathogen reduction technology (PRT). The impact of this process on the structural and biomechanical properties of the final products is unknown. We used normal plasma (PLc) and plasma inactivated by riboflavin and ultraviolet light exposure (PLi) to manufacture nanostructured cellularized fibrin-agarose hydrogels (NFAHs), and then compared their structural and biomechanical properties. We also measured functional protein C, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and coagulation factors [fibrinogen, Factor (F) V, FVIII, FX, FXI, FXIII] in plasma samples before and after inactivation. The use of PLi to manufacture cellularized NFAHs increased the interfibrillar spacing and modified their biomechanical properties as compared with cellularized NFAH manufactured with PLc. PLi was also associated with a significant reduction in functional protein C, FV, FX, and FXI, and an increase in the international normalized ratio (derived from the PT), APTT, and TT. Our findings demonstrate that the use of PRT for fibrin-agarose bioartificial tissue manufacturing does not adequately preserve the structural and biomechanical properties of the product. Further investigations into PRT-induced changes are warranted to determine the applications of NFAH manufactured with inactivated plasma as a medicinal product.Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+i) from Ministerio de Ciencia, Innovación y Universidades (Instituto de Salud Carlos III), grants FIS PI17/0391, RTC-2017- 6658-1, PI20/0317 and ICI19/00024 (BIOCLEFT)Fondo Europeo de Desarrollo Regional ERDF-FEDEREuropean UnionPE-0395-2019 from Consejería de Salud y Familias, Junta de Andalucía, Spai

Evaluation of epithelial–mesenchymal transition markers in autoimmune thyroid diseases

A state of chronic inflammation is common in organs affected by autoimmune disorders, such as autoimmune thyroid diseases (AITD). Epithelial cells, such as thyroid follicular cells (TFCs), can experience a total or partial transition to a mesenchymal phenotype under these conditions. One of the major cytokines involved in this phenomenon is transforming growth factor beta (TGF-β), which, at the initial stages of autoimmune disorders, plays an immunosuppressive role. However, at chronic stages, TGF- β contributes to fibrosis and/or transition to mesenchymal phenotypes. The importance of primary cilia (PC) has grown in recent decades as they have been shown to play a key role in cell signaling and maintaining cell structure and function as mechanoreceptors. Deficiencies of PC can trigger epithelial–mesenchymal transition (EMT) and exacerbate autoimmune diseases. A set of EMT markers (E-cadherin, vimentin, α-SMA, and fibronectin) were evaluated in thyroid tissues from AITD patients and controls through RT-qPCR, immunohistochemistry (IHC), and western blot (WB). We established an in vitro TGF-β–stimulation assay in a human thyroid cell line to assess EMT and PC disruption. EMT markers were evaluated in this model using RT-qPCR and WB, and PC was evaluated with a time-course immunofluorescence assay. We found an increased expression of the mesenchymal markers α-SMA and fibronectin in TFCs in the thyroid glands of AITD patients. Furthermore, E-cadherin expression was maintained in these patients compared to the controls. The TGF-β-stimulation assay showed an increase in EMT markers, including vimentin, α-SMA, and fibronectin in thyroid cells, as well as a disruption of PC. The TFCs from the AITD patients experienced a partial transition to a mesenchymal phenotype, preserving epithelial characteristics associated with a disruption in PC, which might contribute to AITD pathogenesisThis work was supported by the following grants: Proyectos de Investigación en Salud (PI) PI19-00584 and PI22/01404, and Proyectos de investigación de Medicina Personalizada de Precisión (PMP) PMP22/00021 (funded by Instituto de Salud Carlos III); iTIRONET P2022/BMD7379 (funded by Comunidad de Madrid); FEDER funds to M.M and R.M.-H. (cofinanced); predoctoral fellowship funded by Instituto de Salud Carlos III and FSE+ funds (FI20/00035) to P.S.-G; and predoctoral fellowships funded by Comunidad de Madrid (PEJ-2020-AI_BMD-18292) to N.S.d.l.B.C. The funders had no role in the study design, data collection, data analysis, interpretation, or writing of the repor

Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke

Angiogenina; Terapia intensiva; RehabilitaciónAngiogenin; Intensive therapy; RehabilitationAngiogenina; Teràpia intensiva; RehabilitacióBackground: Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation. Objective: To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study. Methods: A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring. Results: The median (IQR) number of weekly hours of therapy was different: IRT 15 (15–16) vs. NO-IRT 7.5 (5–9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05). Conclusions: Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers.NG-R holds a VHIR fellowship and MO-G a Joan Margarit VHIR fellowship. Research grants: from the Instituto de Salud Carlos III and European Regional Development Funds (PI16/00981, PI19/00186, RD16/0019/0021, and RD16/0019/0008), 2017-SGR-1427 program from the Generalitat de Catalunya-AGAUR, and Clinical Translational Program for Regenerative Medicine in Catalonia (P-CMR [C])

Contextualizing Evidence for Action on Diabetes in Low-Resource Settings—Project CEAD Part I: A Mixed-Methods Study Protocol

Challenges remain for policy adoption and implementation to tackle the unprecedented and relentless increase in obesity, diabetes and other non-communicable diseases (NCDs), especially in low- and middle-income countries. The aim of this mixed-methods study is to analyse the contextual relevance and applicability to low-resource settings of a sample of evidence-based healthy public policies, using local knowledge, perceptions and pertinent epidemiological data. Firstly, we will identify and prioritise policies that have the potential to reduce the burden of diabetes in low-resource settings with a scoping review and modified Delphi method. In parallel, we will undertake two cross-sectional population surveys on diabetes risk and morbidity in two low-resource settings in Ecuador. Patients, community members, health workers and policy makers will analyse the contextual relevance and applicability of the policy actions and discuss their potential for the reduction in inequities in diabetes risk and morbidity in their population. This study tackles one of the greatest challenges in global health today: how to drive the implementation of population-wide preventative measures to fight NCDs in low resource settings. The findings will demonstrate how local knowledge, perceptions and pertinent epidemiological data can be used to analyse the contextual relevance and applicability of potential policy actions

Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer

EGFR-mutant non-small cell lung cancer are often resistant to EGFR tyrosine kinase inhibitor treatment. In this study, the authors show that resistant tumors display high Akt activation and that a combined treatment with AKT inhibitors causes synergistic tumour growth inhibition in vitro and in vivo

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy