e24015
Background: Colorectal cancer (CRC) is the second most frequent malignancy in patients (pts) aged 70. Elderly patients are often excluded by clinical trials; however, improvements in quality ...of life and comorbidities management led to expand the access to anticancer treatments irrespectively of age per se. Finding new tools to stratify vulnerability in elderly pts is crucial to guide clinicians in therapeutic decisions. G8 and timed up and go test (TUG) have been related to prognosis and functional decline in patients affected by several solid tumors. However, no studies focused on TUG and G8 prognostic value in CRC pts are available. In this study, we assessed the prognostic value of G8 and TUG in a cohort of real-life elderly pts with metastatic CRC (mCRC). Methods: GOLD was a multicentre, observational, prospective study in which pts aged 70 with mCRC and eligible to 1
st
line therapy were enrolled. G8 and TUG were performed at screening and at the first documented disease progression (PD). G8 cutoff was 14, as reported in literature; TUG8,5 sec (cutoff set with ROC curve using MedCalc software v 20.027). PFS and OS were described with Kaplan-Meyer curve. All analyzed variables were then compared with multivariate models. Primary endpoint of the study was to assess prognostic value of G8 in OS and PFS. Secondary endpoints were to assess prognostic value of TUG in OS and PFS. Results: Since Oct 2017 to Apr 2019, 109 pts were evaluated in 4 different Oncology Units in Veneto (IT); 4 were not eligible to anticancer treatments and where thus excluded. 105 pts were finally enrolled. Clinical, histological and molecular characteristics were well balanced between pts with G814 vs > 14, with the exception of RASmut, more represented in the G8 > 14 group (p = 0,0195). 39 (37%) pts were aged80; 46 (44%) had ECOG PS1; 55 (53%) had RASmut; 15 (15%) had BRAFmut. 81 (77%) had G814; 78 (75%) had TUG8,5. At a median follow up time of 41,2 months, median OS was 19,41 months (95%CI 15,46-23,19) and median PFS 8,78 months (95% CI 7,53-10,07). OS was longer in patients with G814 (HR 0,61; 95%CI 0,39-0,97; p= 0,0584) and TUG8,5 (HR 0,55; 95%CI 0,35- 0,86; p= 0,0201). PFS was not influenced by G8 (HR 0,86; 95%CI 0,55-1,34; p= 0,5125) nor by TUG (HR 0,71; 95%CI 0,47-1,08). G814 and TUG8,5 conferred better OS also in the subgroup of RASmut (respectively p= 0,0133 and p= 0,0088). Worse OS was observed in presence of > 1 metastatic site (HR = 1,71; 95%CI 1,11 to 2,64; p= 0,0161). At the multivariate analysis, G814 ( p= 0,0202) and single metastatic site ( p= 0,0200) were related to better OS; none of the analysed variables had effect on PFS. Conclusions: In our study G814 and TUG8,5 had prognostic value in OS, but not in PFS, in a real-life population of elderly pts affected by mCRC. G8 and single metastatic site involvement were related to better OS, irrespectively of other clinical, histological and molecular variables.
Los árboles han jugado un papel fundamental en el desarrollo de las civilizaciones, tanto como recursos de aprovisionamiento como por otros servicios ecosistémicos. Sin embargo hay una fuerte ...perturbación de los bosques tropicales que ha disminuido la cantidad y diversidad de los árboles. Una de las causas principales de esta situación es el cambio de uso del suelo, sobre todo para actividades ganaderas, que en el estado de Veracruz, México, ocupan alrededor de 3.7 millones de hectáreas (50.6% de su territorio). El objetivo de este trabajo fue investigar el conocimiento que los ganaderos tienen sobre las especies arbóreas, sus usos, su importancia cultural y los cambios que han sucedido a lo largo del tiempo. Se mencionaron 68 especies de árboles y se hizo una clasificación de 22 tipos de usos. Se calculó el índice de importancia cultural de cada especie y se describieron los cambios más importantes en el estilo de vida de las comunidades de estudio. Se encontró que hay un conocimiento amplio sobre los árboles pero se está perdiendo rápidamente. Los árboles se usan no solo para obtener beneficios en la ganadería sino para satisfacer otras necesidades de la vida cotidiana. La cantidad y la diversidad de especies arbóreas refleja el estilo de vida de las comunidades junto con sus influencias y cambios en el tiempo. Las decisiones de los ganaderos configuran el paisaje y por lo tanto se recomienda aumentar la cantidad de árboles en los potreros, su conservación y su uso para mantener los servicios ecosistémicos que proveen.
As tecnologias da informação e comunicação (TICs) tornaram possível o aparecimento de um ambiente interat ivo, cooperat ivo e descent ral izado, desenhando perspectivas ousadas nas relações entre ...pessoas, comunidades e governos. Atualmente, as manifestações sociais, organizadas com o apoio dessas tecnologias, podem se fazer ouvir e ter suas reivindicações atendidas em um ambiente até então permeado por uma mídia de massa vertical, que sempre falou em nome de uma minoria para uma maioria, sem qualquer possibilidade de interação. O uso dessas ferramentas pela sociedade civil traz profundas transformações para a ação coletiva contemporânea, e assim, o objetivo deste trabalho é discutir como, e até que ponto, esta nova realidade possibilitará a participação dos cidadãos nos processos democráticos. Para tanto, buscou-se primeiramente refletir sobre o processo de comunicação e sua relação com a sociedade, como se configura o ciberespaço, as possibilidades por ele oferecidas e suas implicações nos movimentos sociais. Foram elaborados quatro estudos de caso: “Movimento Zapatista”, “A Noite dos Celulares”, “Rua Gonçalo de Carvalho” e “Pontal do Estaleiro”. Eventos com motivações, contextos, abrangência e formas de atuação bem diferentes, que através de trocas de informação disseminadas no ambiente online foram capazes de mobilizar a adesão dos cidadãos em torno de projetos de interesse comum. Os impactos sociais e políticos dessa comunicação mostram que apesar de restrições estruturais, o uso das tecnologias permite formas inovadoras de exercício da democracia. O trabalho demonstrou que as TICs podem ser pensadas como um “ciberespaço público”, sem no entanto atribuir a sua mera existência a promessa de uma sociedade mais democrática.
Information and communications technologies (ICT) have allowed the emergence of an interactive, collaborative and decentralized environment, bringing together audacious perspectives in relationships among people, communities and governments. Nowadays, social events organized by ICTs supports have their claims attended in environment that before it was permeated by a vertical mass media. Media which has always spoken on behalf of a minority to a majority, without interaction possibilities. The use of ICTs tools by civil society brings huge changes to the contemporary collective action. Then main challenge of this work is to discuss how and whither this new reality will allow the people participation in democratic processes. For this purpose, we first think about the communication process and their relation with the society. We also consider the way in which the cyberspace is configured, its possibilities and its implications for social movements. We have specified four case studies: "Zapatista Movement", “Night of cell phones”, "Gonçalo de Carvalho Street", and "Shipyard Pontal". All this events have motivation, context, scope and ways of acting different once that through information exchanges spread in the online environment allowed mobilize people around projects with common interest. The social and political impacts of this communication have shown that despite structural constraints, the use of new technologies allow innovative ways of exercising democracy. Our work prove that ICTs can be thought as a "public cyberspace”, without assign its mere existence for the promise of the a more democratic society.
As tecnologias da informação e comunicação (TIC) tornaram possível o aparecimento de um ambiente interativo, cooperativo e descentralizado. O uso dessas ferramentas pela sociedade civil traz ...profundas transformações para a ação coletiva contemporânea, e assim, o objetivo deste trabalho é discutir como, e até que ponto, essa realidade possibilitará a participação dos cidadãos nos processos democráticos. Para tanto, o trabalho apresenta dois estudos de caso: “Rua Gonçalo de Carvalho” e “Pontal do Estaleiro” e demonstram que as TICs podem ser pensadas como um “ciberespaço público”, sem, no entanto, atribuir a sua mera existência a promessa de uma sociedade mais democrática.
As tecnologias da informação e comunicação (TIC) tornarampossíveloaparecimento de um ambiente interativo, cooperativo e descentralizado. O uso dessas ferramentas pela sociedade civil traz profundas ...transformações para a ação coletiva contemporânea, e assim, o objetivo deste trabalho é discutir como, e até que ponto, essa realidade possibilitará a participação dos cidadãos nos processos democráticos. Para tanto, o trabalho apresenta dois estudos de caso: “Rua Gonçalo de Carvalho” e “Pontal do Estaleiro” e demonstram que as TICs podem ser pensadas como um “ciberespaço público”, sem, no entanto, atribuir a sua mera existência a promessa de uma sociedade mais democrática.
A new low‐energy pathway is reported for the electrochemical reduction of CO2 to formate and syngas at low overpotentials, utilizing a reactive ionic liquid as the solvent. The superbasic tetraalkyl ...phosphonium ionic liquid P66614124Triz is able to chemisorb CO2 through equimolar binding of CO2 with the 1,2,4‐triazole anion. This chemisorbed CO2 can be reduced at silver electrodes at overpotentials as low as 0.17 V, forming formate. In contrast, physically absorbed CO2 within the same ionic liquid or in ionic liquids where chemisorption is impossible (such as P66614NTf2) undergoes reduction at significantly increased overpotentials, producing only CO as the product.
The superbasic RTIL (room‐temperature ionic liquid) P66614124Triz provides an alternative low‐energy pathway for conversion of CO2 into formate. This is the first time chemical binding of the CO2 molecule to the anion of a RTIL has been shown to decrease the activation energy for electrochemical reduction, by distortion of the CO2 geometry from linear to bent.
E‐mail: ilaria.piano@unipi.it.
Retinal diseases can be induced by several factors, including genetic mutations, environmental stresses, and dysmetabolic processes. The result is a progressive loss of ...visual function, that can leading to total blindness. Among the diseases still orphaned of an effective therapy for slowing retinal degeneration is Retinitis Pigmentosa (RP). RP is one of the inherited retinal degenerative diseases (IRDs) whose cause is attributed to genetic mutations mainly at the level of rod‐specific genes. To date, about 150 mutations out of 60 different genes have been identified.
Several therapeutic strategies are being investigated, although the results are still mostly unsatisfactory and limited to specific diseases, particularly in the case of gene therapy, which is applicable only to specific mutations and therefore not applicable on a large scale. Most of the proposed treatments have been tested in animal models, but few have progressed to human clinical trials. An important approach is to identify targets at the level of those mechanisms that are in common in all forms of RP and that drive disease progression, such as stress‐oxidative and inflammation that all together are known as oxinflammation. Here we provide data showing that in RP natural compounds are effective in slowing down the progression of the disease mainly counteracting oxinflammation. Specifically, saffron “Repron” was proved to be effective in AMD and Stargardt patients as well as in pre‐clinical models both “in vitro” and “in vivo.” We tested this treatment in a IRD model. Preliminary obtained in an animal model of RP (rd10 mice) where saffron treatment was able to slow down even the degeneration of rod due to a genetic mutation. In this study, the treatment began in rd10 pregnant females and continued throughout the weaning phase and then in pups that had become autonomous. Functional, immunohistochemical, molecular biology and biochemical analyses were performed at multiple time points from P20 to P120. The results obtained show a protective effect of saffron on both retinal function and morphology, opening a prospect of preventive treatment for those inherited diseases whose progression is known.
Parkinson's Disease is the second most common neurodegenerative disorder, affecting 1-2% of the elderly population. Its diagnosis is still based on the identification of motor symptoms when a ...considerable number of dopaminergic neurons are already lost. The development of translatable biomarkers for accurate diagnosis at the earliest stages of PD is of extreme interest. Several microRNAs have been associated with PD pathophysiology. Consequently, microRNAs are emerging as potential biomarkers, especially due to their presence in Cerebrospinal Fluid and peripheral circulation. This study employed small RNA sequencing, protein binding ligand assays and machine learning in a cross-sectional cohort comprising 40 early stage PD patients and 40 well-matched controls. We identified a panel comprising 5 microRNAs (Let-7f-5p, miR-27a-3p, miR-125a-5p, miR-151a-3p and miR-423-5p), with 90% sensitivity, 80% specificity and 82% area under the curve (AUC) for the differentiation of the cohorts. Moreover, we combined miRNA profiles with hallmark-proteins of PD and identified a panel (miR-10b-5p, miR-22-3p, miR-151a-3p and α-synuclein) reaching 97% sensitivity, 90% specificity and 96% AUC. We performed a gene ontology analysis for the genes targeted by the microRNAs present in each panel and showed the likely association of the models with pathways involved in PD pathogenesis.
Complex oxides can present interesting semiconductor properties since the simultaneous presence of different metallic cations can modulate the conduction and valence band edges, affecting the bandgap ...energy, the onset potential for reactions and also the photocatalyst long-term stability. Here, we demonstrated that the synthesis of multinary oxides, very challenging using “traditional” methodologies, can be fast achieved by melting the precursor binary oxides in an arc furnace. As a proof of concept, arc-melting a mixture of Bi2O3 and V2O5 (Bi:V molar ratio of 1:1.05) resulted in almost pristine BiVO4 (97.3% from Rietveld refinement of X-ray diffraction (XRD) data); photoelectrochemical (PEC) measurements indicated a promising application as a photoanode for O2 evolution reaction. Conversely, the arc-melting of Bi2O3 and WO3 mixture (Bi:W molar ratio of 2:1.15) resulted in the biphasic Bi2WO6/Bi2W2O9; preliminary PEC analysis revealed characteristics of n-type semiconductor electrode with photoactivity under UV irradiation. Finally, the hierarchical Ag@α-AgVO3/Fe2O3 consisted of micrometric Fe2O3 particles decorated by AgVO3 nanoribbons and Ag nanoparticles, was obtained from melting Ag2O, Fe2O3 and V2O5 as precursors (Ag:Fe:V molar ratio of 3:1:2); PEC measurements also revealed possible application as a photoanode. The results for these three materials demonstrated the arc-synthesis as a fast, effective and scalable methodology for synthesizing complex oxides.
Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common ...worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer's Disease, Parkinson's Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis.
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