The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis.

BACKGROUND: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis. PATIENTS AND METHODS: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists. RESULTS: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd. CONCLUSIONS: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.

Hatching Asynchrony in Oviraptorid Dinosaurs Sheds Light on Their Unique Nesting Biology.

Dinosaur nesting biology has been an intriguing research topic, though dinosaur behaviors were relatively less illuminated because of the constraints of the fossil record. For instance, hatching asynchrony, where eggs in a single clutch hatch at different times, is unique to modern neoavian birds but was also suggested to be present in oviraptorid dinosaurs based on a possible partial clutch of four embryo-containing eggs from Mongolia. Unfortunately, unequivocal evidence for the origination of these eggs from a single clutch is lacking. Here we report a new, better preserved partial oviraptorid clutch with three embryo-containing eggs-a single egg (Egg I) and a pair (Egg II/III)-from the Late Cretaceous Nanxiong Group of Jiangxi Province, China. Geopetal features indicate that the pair of eggs was laid prior to the single egg. Neutron tomographic images in combination with osteological features indicate that the embryo of the single egg is less developed than those of the paired eggs. Eggshell histology suggests that the embryo-induced erosion in the paired eggs is markedly more pronounced than in the single egg, providing a new line of evidence for hatching asynchrony. The inferred hatching asynchrony in combination with previously surmised thermoregulatory incubation and communal nesting behaviors very likely suggests that oviraptorid dinosaurs presented a unique reproductive biology lacking modern analogs, which is contrary to the predominant view that their reproductive biology was intermediate between that of modern crocodiles and birds.

A biologia de nidificação de dinossauros tem sido um tópico de pesquisa intrigante, embora o comportamentos do dinossauros tenham sido relativamente menos compreendidos devido às restrições do registro fóssil. Por exemplo, eclosão assincrônica, onde os ovos em uma única ninhada eclodem em momentos diferentes, é exclusiva em aves neoavianas modernas, tem-se sugerido estar presente em dinossauros oviraptorídeos com base em uma possível ninhada parcial de quatro ovos da Mongólia contendo embriões. Infelizmente, faltam evidências inequívocas para a origem desses ovos a partir de uma única embreagem. Relatamos aqui uma nova parcial ninhada oviraptoroide melhor preservada, com três ovos contendo embriões­um único ovo (ovo I) e um par (ovo II/III)­do Grupo de Nanxiong Cretáceo Final da Província de Jiangxi, China. A erosão induzida pelo embrião nos ovos emparelhados é significativamente maior que a do ovo único, fornecendo uma evidência inequívoca de eclosão assincrônica. A inferida de eclosão assincrônica, em combinação com as linhas de evidência anteriores, sugere que os dinossauros oviraptorídeos apresentavam uma biologia reprodutiva muito singular, sem análogos modernos, contrariando a visão predominante de que sua biologia reprodutiva era intermediária entre a dos crocodilos e pássaros modernos. Translated to Portuguese by Diego Vaz (dbistonvaz@vims.edu).

Substitution of blood coagulation factor X-binding to Ad5 by position-specific PEGylation: Preventing vector clearance and preserving infectivity.

The biodistribution of adenovirus type 5 (Ad5) vector particles is heavily influenced by interaction of the particles with plasma proteins, including coagulation factor X (FX), which binds specifically to the major Ad5 capsid protein hexon. FX mediates hepatocyte transduction by intravenously-injected Ad5 vectors and shields vector particles from neutralization by natural antibodies and complement. In mice, mutant Ad5 vectors that are ablated for FX-binding become detargeted from hepatocytes, which is desirable for certain applications, but unfortunately such FX-nonbinding vectors also become sensitive to neutralization by mouse plasma proteins. To improve the properties of Ad5 vectors for systemic delivery, we developed a strategy to replace the natural FX shield by a site-specific chemical polyethylene glycol shield. Coupling of polyethylene glycol to a specific site in hexon hypervariable region 1 yielded vector particles that were protected from neutralization by natural antibodies and complement although they were unable to bind FX. These vector particles evaded macrophages in vitro and showed significantly improved pharmacokinetics and hepatocyte transduction in vivo. Thus, site-specific shielding of Ad5 vectors with polyethylene glycol rendered vectors FX-independent and greatly improved their properties for systemic gene therapy.

Ingesta de macronutrientes y prevalencia de malnutrición por exceso en escolares de 5º y 6º básico de distinto nivel socioeconómico de la Región Metropolitana / Macronutrients intake and overweight prevalence in 5th and 6th grade of socioeconomic levels in the Metropolitan Region

Obesity in childhood has become an important public health problem in Chile. Objective: to study macronutrient intake and nutritional status in school-age children attending5th and 6th grade in primary schools from different socioeconomic status located in 6 counties in Santiago, Chile. Methods: A total of 1,732 children between 9 and 12 years old jrom both sexes were studied. Anthropometric evaluation included weight, height, and tricipital and subescapular thickness. Macronutrient intake was determined using a 24-hours recall survey. Socioeconomic status was estimated using the ESOMAR survey. Results: In this sample overweight and obesity prevalence reached 40 percent. Prevalence was higher in boys and in the lower socio-economic groups. A higher consumption of proteins and fat was found in the wealthier groups, while a higher intake of carbohydrates was present in the poorer ones. Comparison with the daily recommended allow ances found that both males and females had a 75 percent of adequacy of all of macronutrients with the exception of fiber. Conclusion: The study revealed a high prevalence of malnutrition in both sexes with a better nutrition standard among children in higher socioeconomic status.

El sobrepeso y la obesidad infantil se han transformado en un importante problema en salud pública. Objetivo: evaluar la ingesta de macronutrientes y determinar la prevalencia de malnutrición en escolares de 5° y 6º año básico de distintos niveles socioeconómicos de 6 comunas de la Región Metropolitana. Sujetos y método: se evaluaron 1732 niños de ambos sexos de 9 a 12 años de edad. La evaluación antropométrica incluyo peso, talla, pliegue tricipital y subescapular. La ingesta de macronutrientes se evaluó mediante la aplicación de una encuesta recordatorio de 24 hrs; el nivel socioeconómico se evaluó mediante la aplicación la encuesta ESOMAR. Resultados: la prevalencia de malnutrición por exceso fue de 40 por ciento, siendo más importante en hombres de los estratos socioeconómicos de menores ingresos. Encontramos un mayor consumo de proteínas y grasas totales en el nivel socioeconómico más alto, mientras que el nivel de menores ingresos tuvo una mayor ingesta de carbohidratos. Tanto hombres como mujeres presentaron una adecuación superior al 75 por ciento en todos los macronutrientes con excepción de la fibra. Conclusión: El estudio arrojó una elevada prevalencia de malnutrición por exceso en ambos sexos con un mejor patrón de alimentación en los niños de nivel socioeconómico alto.

Stereoselective syntheses of substituted pterocarpans with anti-HIV activity, and 5-aza-/5-thia-pterocarpan and 2-aryl-2,3-dihydrobenzofuran analogues.

Oxygenated pterocarpans and 5-azapterocarpans are prepared utilizing Lewis acid-promoted reactions of 2-alkoxy-1,4-benzoquinones with 2H-chromenes and N-tosyl-1,2-dihydroquinolines, respectively. Similarly, benzannulated analogues are prepared via reactions of 5-alkoxy-1,4-naphthoquinones with chromenes, and related 2-aryl-2,3-dihydrobenzofurans result from reactions of styrenes with the quinones. Syntheses of 5-thiapterocarpans are also described utilizing Pd(0)-coupling of o-chloromercuriophenols with 2H-chromenes.

[The general practitioner and community medical services]. / El médico general y los servicios médicos a la comunidad.

The writer defines the role of the general practitioner in the setting of the health system of Panama and in relation to the individual, the family and the community, in the framework of the policy of extending the coverage of health services to the entire population. He stresses that modern medicine has to focus on the whole person, and he concludes therefrom that the physician must be prepared to provide comprehensive care. He emphasizes that, to overcome the limitations that now weigh upon medical education, in the internship stage the training of the general practitioner must begin at the level of a specialty and be completed later with two or three years of theoretical and practical instruction. This requires strengthened instruction in comprehensive outpatient care, extensive contact with rural and urban communities, and that teaching programs be set in the framework of the health services and facilities. He also feels that the general physician already practicing should be offered the opportunity of qualifying under an in-service education program as a specialist in comprehensive, general or family medicine, with a certification system that includes the approval of academic studies and the performance of research work.

Production of erythroid potentiating factor(s) by a human monocytic cell line.

U-937 is a human monocytic cell line that has been to elaborate factors that affect normal human hematopoiesis in vitro. Studies on the effects of these factors demonstrated an erythroid potentiating factor (EPF) and a potent inhibitor of granulocyte-macrophage (CFU-GM) colony growth. The EPF was present in both serum-containing and serum-free U-937 conditioned media, had a dose-dependent effect on erythroid colony formation and was remarkably heart stable. The CFU-GM inhibitory activity was also detected in serum-free conditioned medium, was dose-dependent, heart labile and its effect was reversed by Indomethacin. Indomethacin (Sigma, St. Louis, Mo.) did not alter the erythroid effects of the U-937 conditioned medium. No colony stimulating factor (CSF) or erythropoietin (Ep) could be detected in this medium. The existence of a human cell line capable of production EPF without simultaneous CSF production will permit further studies on the biochemical and biologic nature of these factors.