Para fortalecer el ‘cómo hacer’: una caja de herramientas virtual para entornos saludables

Introducción: Según Paulo Freire, un eminente educador brasileño, “la teoría sin la práctica se torna ‘verbalismo’, así como la practica sin la teoría, se torna activismo. Sin embargo, cuando la práctica se une a la teoría, tenemos la ´praxis´: la acción creadora y modificadora de la realidad”. Cada vez más se fortalece la teoría sobre las prácticas saludables, sin embargo siguen las brechas sobre el cómo hacer´, para que estas teorías se traduzcan en prácticas con potencial para la transformación de la realidad. Este trabajo presenta una propuesta de una caja de herramientas virtual para fortalecer la práctica de los actores en el campo de la formulación de las políticas públicas saludables. Material y método: Como parte de una Carta Acuerdo firmada en 2015 entre el Ministerio de Salud y Protección Social de Colombia, la Organización Panamericana de la Salud de Colombia, y el Centro de Pesquisa e Documentação em Cidades Saudáveis (CEPEDOC), se desarrolló una caja de herramientas virtual basada en una amplia revisión de la literatura, consulta con expertos y revisión de herramientas existentes en inglés, español y portugués para identificar materiales que aborden de forma práctica la implementación de entornos saludables. Este es una iniciativa aún en construcción; seguiremos incluyendo materiales que se identifiquen como relevantes. Resultados: La Caja de Herramientas es de libre acceso y está disponible en el sitio web http://www.cidadessaudaveis.org.br/herramientas/. Está organizada en ocho temas: actividad física, ecosistema, entornos comunitarios, entorno educativo, entornos vivienda, entorno laboral, envejecimiento y municipios saludables. Actualmente cuenta con 51 materiales de aplicación práctica. Conclusiones: Esta es una iniciativa aún en desarrollo. Se espera que su diseminación y divulgación permita ampliar su alcance y colaborar para cerrar la brecha sobre el ‘cómo hacer’ de las prácticas y políticas saludables

Implementation of 26 Gy in five fractions over 1 week adjuvant radiotherapy for breast cancer: Prospective report of acute skin toxicity and consideration of resource implications

Purpose: In March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity. Materials and methods: This is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar–Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use. Results: In total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule. Conclusion: Rapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost

Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis.

Pregnancy reprograms mammary epithelial cells (MECs) to control their responses to pregnancy hormone re-exposure and carcinoma progression. However, the influence of pregnancy on the mammary microenvironment is less clear. Here, we used single-cell RNA sequencing to profile the composition of epithelial and non-epithelial cells in mammary tissue from nulliparous and parous female mice. Our analysis indicates an expansion of γδ natural killer T-like immune cells (NKTs) following pregnancy and upregulation of immune signaling molecules in post-pregnancy MECs. We show that expansion of NKTs following pregnancy is due to elevated expression of the antigen-presenting molecule CD1d on MECs. Loss of CD1d expression on post-pregnancy MECs, or overall lack of activated NKTs, results in mammary oncogenesis. Collectively, our findings illustrate how pregnancy-induced changes modulate the communication between MECs and the immune microenvironment and establish a causal link between pregnancy, the immune microenvironment, and mammary oncogenesis

PELP1/SRC-3-dependent regulation of metabolic PFKFB kinases drives therapy resistant ER+ breast cancer.

Recurrence of metastatic breast cancer stemming from acquired endocrine and chemotherapy resistance remains a health burden for women with luminal (ER+) breast cancer. Disseminated ER+ tumor cells can remain viable but quiescent for years to decades. Contributing factors to metastatic spread include the maintenance and expansion of breast cancer stem cells (CSCs). Breast CSCs frequently exist as a minority population in therapy resistant tumors. In this study, we show that cytoplasmic complexes composed of steroid receptor (SR) co-activators, PELP1 and SRC-3, modulate breast CSC expansion through upregulation of the HIF-activated metabolic target genes PFKFB3 and PFKFB4. Seahorse metabolic assays demonstrated that cytoplasmic PELP1 influences cellular metabolism by increasing both glycolysis and mitochondrial respiration. PELP1 interacts with PFKFB3 and PFKFB4 proteins, and inhibition of PFKFB3 and PFKFB4 kinase activity blocks PELP1-induced tumorspheres and protein-protein interactions with SRC-3. PFKFB4 knockdown inhibited in vivo emergence of circulating tumor cell (CTC) populations in mammary intraductal (MIND) models. Application of PFKFB inhibitors in combination with ER targeted therapies blocked tumorsphere formation in multiple models of advanced breast cancer including tamoxifen (TamR) and paclitaxel (TaxR) resistant models, murine tumor cells, and ER+ patient-derived organoids (PDxO). Together, our data suggest that PELP1, SRC-3, and PFKFBs cooperate to drive ER+ tumor cell populations that include CSCs and CTCs. Identifying non-ER pharmacological targets offers a useful approach to blocking metastatic escape from standard of care ER/estrogen (E2)-targeted strategies to overcome endocrine and chemotherapy resistance