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ObjectiveWe investigated whether there are differences in cancer incidence by geographical area of origin in North-eastern Italy.MethodsWe selected all incident cases recorded in the Veneto Tumour Registry in the period 2015-2019. Subjects were classified, based on the country of birth, in six geographical areas of origin (Italy, Highly Developed Countries-HDC, Eastern Europe, Asia, Africa, South-central America). Age-standardized incidence rates and incidence rate ratio (IRR) were calculated, for all cancer sites and for colorectal, liver, breast and cervical cancer separately.ResultsWe recorded 159,486 all-site cancer cases; 5.2% cases occurred in subjects born outside Italy, the majority from High Migratory Pressure Countries (HMPC) (74.3%). Incidence rates were significantly lower in subjects born in HMPC in both sexes. Immigrants, in particular born in Asia and Africa, showed lower rates of all site cancer incidence. The lowest IRR for colorectal cancer was observed in males from South-Central America (IRR 0.19, 95%CI 0.09-0.44) and in females from Asia (IRR 0.32, 95%CI 0.18-0.70). The IRR of breast cancer appeared significantly lower than Italian natives in all female populations, except for those coming from HDC. Females from Eastern Europe showed a higher IRR for cervical cancer (IRR 2.02, 95%CI 1.57-2.61).ConclusionCancer incidence was found lower in subjects born outside Italy, with differences in incidence patterns depending on geographical area of origin and the cancer type in question. Further studies, focused on the country of birth of the immigrant population, would help to identify specific risk factors influencing cancer incidence.

Abstract Branched chain amino acid (BCAA) catabolic impairments have been implicated in several diseases. Branched chain ketoacid dehydrogenase (BCKDH) controls the rate limiting step in BCAA degradation, the activity of which is inhibited by BCKDH kinase (BDK)-mediated phosphorylation. Screening efforts to discover BDK inhibitors led to identification of thiophene PF-07208254, which improved cardiometabolic endpoints in mice. Structure-activity relationship studies led to identification of a thiazole series of BDK inhibitors; however, these inhibitors did not improve metabolism in mice upon chronic administration. While the thiophenes demonstrated sustained branched chain ketoacid (BCKA) lowering and reduced BDK protein levels, the thiazoles increased BCKAs and BDK protein levels. Thiazoles increased BDK proximity to BCKDH-E2, whereas thiophenes reduced BDK proximity to BCKDH-E2, which may promote BDK degradation. Thus, we describe two BDK inhibitor series that possess differing attributes regarding BDK degradation or stabilization and provide a mechanistic understanding of the desirable features of an effective BDK inhibitor.

Abstract Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone receptor 2 (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of UCN2 induces systemic insulin resistance in male mice and skeletal muscle. Inversely, chronic elevation of UCN2 by injection with adenovirus encoding UCN2 resolves metabolic complications, improving glucose tolerance. CRHR2 recruits Gs in response to low concentrations of UCN2, as well as Gi and β-Arrestin at high concentrations of UCN2. Pre-treating cells and skeletal muscle ex vivo with UCN2 leads to internalization of CRHR2, dampened ligand-dependent increases in cAMP, and blunted reductions in insulin signaling. These results provide mechanistic insights into how UCN2 regulates insulin sensitivity and glucose metabolism in skeletal muscle and in vivo. Importantly, a working model was derived from these results that unifies the contradictory metabolic effects of UCN2.

El comportamiento sexual íntimo de las parejas (normales o no-patológicas) deben ser descritos por los psicólogos, para ello usan dos perspectivas; una es la primera a) psicopatológica del DSM 5 y CIE-10 o, la segunda b) la perspectiva de la psicología positiva, que utilizan los modelos de Kinsey (1953), Masters y Johnson (1966), Kaplan (1979), Schnarch (1991), Whipple y Brash-Mc.Greer (1997), y Basson (2000). Un panel de expertos buscó validar una nueva taxonomía de conductas eróticas. La música sexual se refiere a la conducta individual y diádica que una pareja hace para llegar al coito sexual; las cualidades de la conducta monódica de un amante son: a) Intensidad, b) Duración, c) Timbre y d) Tono sexual; y la coordinación musical diádica de dos amantes son: x) Ritmo, y) Melodía y z) Armonía sexual. Un panel de siete expertos usando el método Delphi validó el contenido de la teoría siete dimensiones de la música sexual proporcionando la definición conceptual y la operacionalización de las variables sexuales usadas; además, los expertos proporcionaron la casuística clínica de sus casos particulares.

The SPES (Selective Production of Exotic Species) facility, currently under development at Legnaro National Laboratories of INFN, aims at the production of intense RIB (Radioactive Ion Beams) employing the Isotope Separation On-Line (ISOL) technique for interdisciplinary research. The radioactive isotopes of interest are produced by the interaction of a multi-foil uranium carbide target with a 40 MeV 200 μA proton beam generated by a cyclotron proton driver. The Target Ion Source (TIS) is the core of the SPES project, here the radioactive nuclei, mainly neutron-rich isotopes, are stopped, extracted, ionized, separated, accelerated and delivered to specific experimental areas. Due to efficiency reasons, the TIS unit needs to be replaced periodically during operation. In this highly radioactive environment, the employment of autonomous systems allows the manipulation, transport, and storage of the TIS unit without the need for human intervention. A dedicated remote handling infrastructure is therefore under development to fulfill the functional and safety requirement of the project. This contribution describes the layout of the SPES target area, where all the remote handling systems operate to grant the smooth operation of the facility avoiding personnel exposure to a high dose rate or contamination issues.

This article investigates the strategies modern-day autocrats use to delegitimate the press as a means of consolidating power, including in democratic states. Using content analysis and Brazil as a case study, I examine Bolsonaro's online discourse on X and YouTube, during the second half of his administration (January 2021–December 2022). I argue that Bolsonaro endeavors to promote an image of the press that centers on three elements: unreliability, obsolescence, and being an enemy to the people. The delegitimation of the press through discursive, insidious means suggests a change in the way autocrats exercise power. Rather than deploying the repressive tactics of old, modern autocrats are updating their toolbox to monopolize power while enjoying the legitimacy normally granted by democratic norms. These findings raise questions about the dispersion of authoritarian practices in supposed democracies. [ABSTRACT FROM AUTHOR]

Em 1996, a historiadora da biologia norte-americana Vassiliki Betty Smocovitis publicou um livro de leitura obrigatória para se conhecer a história da biologia do século XX: Unifying biology: the evolutionary synthesis and evolutionary biology. Embora o subtítulo indique o recorte do evento histórico das décadas de 1930 e 1940, que levou à então chamada síntese moderna ou teoria sintética de evolução, o livro perpassa diversas subáreas das ciências biológicas, incluindo as que ficaram de fora da mencionada teoria. Também mais do que o já trivial relato dos feitos dos “arquitetos” da síntese, Smocovitis ofereceu uma interpretação historiograficamente nova. Em vez de ápice de um processo quase espontâneo, cumulativo e linear, a autora coloca a síntese como um “alvo móvel”, mas de longa data desejado, o da unificação da ciência, nutrido pelas “ciências positivas” do século XIX e definitivamente marcado pelo empirismo lógico das primeiras décadas do século XX. Após contextualizar o ponto de partida dos entrevistadores em meio à pandemia da covid-19 e sumarizar os assuntos acima referidos, o presente artigo traz entrevista realizada virtualmente com a autora em 17 de novembro de 2021. Além dos temas abordados, pudemos conhecer um pouco mais sobre como a autora concebeu a obra e como transcorreu o processo de escrita do seu Unifying biology. Interessou-nos especialmente que ela discorresse sobre o forte contextualismo que renovou a história das ciências nos anos 1990 e hoje passa, por vezes, ignorado dos jovens pesquisadores da área. Nosso interesse foi explorar como ela combinou seu profundo conhecimento da história da biologia e da sua historiografia com as novas tendências dos science studies. Outros tópicos acabaram trazidos à conversa, como o dos paradigmas teóricos subjacentes à história e filosofia da biologia, do estado atual da institucionalização da história das ciências nos EUA, dos entraves da popularização da ciência e do impacto dos governos autoritários na atividade acadêmica.