Financial and Other Life Stressors, Psychological Distress, and Food and Beverage Consumption among Students Attending a Large California State University during the COVID-19 Pandemic.

The novel coronavirus disease 2019 (COVID-19) pandemic abruptly disrupted the daily lives and health of college students across the United States. This study investigated several stressors (e.g., financial strain/uncertainty), psychological distress, and dietary behaviors among college students attending a large state university during the pandemic. A cross-sectional online survey was administered to students from the California State University, Los Angeles between April and May 2021 (final analytic sample n = 736). Differences in gender and race/ethnicity were examined using chi-square, t-test, and one-way ANOVA tests. Paired t-tests were performed to compare variables before and during the pandemic. Negative binomial regression models examined the associations between various stressors, psychological distress, and three key dietary outcomes. Descriptive results showed that the consumption of fruits and vegetables, fast food, and sugary beverages, along with psychological distress, all increased during the pandemic. Significant differences in fruit and vegetable and fast food consumption by gender and race/ethnicity were also observed. In the regression models, several stressors, including financial strain and psychological distress, were associated with unfavorable food and beverage consumption, thereby suggesting that college students may need more support in mitigating these stressors so they do not manifest as poor dietary behaviors. Poor diet quality is associated with poor physical health outcomes such as premature development of type 2 diabetes or hypertension.

Neuropilin 1 regulates bone marrow vascular regeneration and hematopoietic reconstitution.

Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche wherein hematopoietic stem cells reside. Hematopoietic stem cell regeneration requires signaling from an intact bone marrow (BM) vascular niche, but the mechanisms that control BM vascular niche regeneration are poorly understood. We report that BM vascular endothelial cells secrete semaphorin 3 A (SEMA3A) in response to myeloablation and SEMA3A induces p53 - mediated apoptosis in BM endothelial cells via signaling through its receptor, Neuropilin 1 (NRP1), and activation of cyclin dependent kinase 5. Endothelial cell - specific deletion of Nrp1 or Sema3a or administration of anti-NRP1 antibody suppresses BM endothelial cell apoptosis, accelerates BM vascular regeneration and concordantly drives hematopoietic reconstitution in irradiated mice. In response to NRP1 inhibition, BM endothelial cells increase expression and secretion of the Wnt signal amplifying protein, R spondin 2. Systemic administration of anti - R spondin 2 blocks HSC regeneration and hematopoietic reconstitution which otherwise occurrs in response to NRP1 inhibition. SEMA3A - NRP1 signaling promotes BM vascular regression following myelosuppression and therapeutic blockade of SEMA3A - NRP1 signaling in BM endothelial cells accelerates vascular and hematopoietic regeneration in vivo.

Epidermal growth factor receptor-dependent DNA repair promotes murine and human hematopoietic regeneration.

Chemotherapy and irradiation cause DNA damage to hematopoietic stem cells (HSCs), leading to HSC depletion and dysfunction and the risk of malignant transformation over time. Extrinsic regulation of HSC DNA repair is not well understood, and therapies to augment HSC DNA repair following myelosuppression remain undeveloped. We report that epidermal growth factor receptor (EGFR) regulates DNA repair in HSCs following irradiation via activation of the DNA-dependent protein kinase-catalytic subunit (DNA-PKcs) and nonhomologous end joining (NHEJ). We show that hematopoietic regeneration in vivo following total body irradiation is dependent upon EGFR-mediated repair of DNA damage via activation of DNA-PKcs. Conditional deletion of EGFR in hematopoietic stem and progenitor cells (HSPCs) significantly decreased DNA-PKcs activity following irradiation, causing increased HSC DNA damage and depressed HSC recovery over time. Systemic administration of epidermal growth factor (EGF) promoted HSC DNA repair and rapid hematologic recovery in chemotherapy-treated mice and had no effect on acute myeloid leukemia growth in vivo. Further, EGF treatment drove the recovery of human HSCs capable of multilineage in vivo repopulation following radiation injury. Whole-genome sequencing analysis revealed no increase in coding region mutations in HSPCs from EGF-treated mice, but increased intergenic copy number variant mutations were detected. These studies demonstrate that EGF promotes HSC DNA repair and hematopoietic regeneration in vivo via augmentation of NHEJ. EGF has therapeutic potential to promote human hematopoietic regeneration, and further studies are warranted to assess long-term hematopoietic effects.

Improved Efficacy and Reduced Toxicity Using a Custom-Designed Irinotecan-Delivering Silicasome for Orthotopic Colon Cancer.

Irinotecan is a key chemotherapeutic agent for the treatment of colorectal (CRC) and pancreatic (PDAC) cancer. Because of a high incidence of bone marrow and gastrointestinal (GI) toxicity, Onivyde (a liposome) was introduced to provide encapsulated irinotecan (Ir) delivery in PDAC patients. While there is an ongoing clinical trial (NCT02551991) to investigate the use of Onivyde as a first-line option to replace irinotecan in FOLFIRINOX, the liposomal formulation is currently prescribed as a second-line treatment option (in combination with 5-fluorouracil and leucovorin) for patients with metastatic PDAC who failed gemcitabine therapy. However, the toxicity of Onivyde remains a concern that needs to be addressed for use in CRC as well. Our goal was to custom design a mesoporous silica nanoparticle (MSNP) carrier for encapsulated irinotecan delivery in a robust CRC model. This was achieved by developing an orthotopic tumor chunk model in immunocompetent mice. With a view to increase the production volume and to expand the disease applications, the carrier design was improved by using an ethanol exchange method for coating of a supported lipid bilayer (LB) that entraps a protonating agent. The encapsulated protonating agent was subsequently used for remote loading of irinotecan. The excellent irinotecan loading capacity and stability of the LB-coated MSNP carrier, also known as a "silicasome", previously showed improved efficacy and reduced toxicity when compared to an in-house liposomal carrier in a PDAC model. Intravenous injection of the silicasomes in a well-developed orthotopic colon cancer model in mice demonstrated improved pharmacokinetics and tumor drug content over free drug and Onivyde. Moreover, improved drug delivery was accompanied by substantially improved efficacy, increased survival, and reduced bone marrow and GI toxicity compared to the free drug and Onivyde. We also confirmed that the custom-designed irinotecan silicasomes outperform Onivyde in an orthotopic PDAC model. In summary, the Ir-silicasome appears to be promising as a treatment option for CRC in humans based on improved efficacy and the carrier's favorable safety profile.

Tumor-penetrating peptide enhances transcytosis of silicasome-based chemotherapy for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD. In a KRAS-induced orthotopic PDAC model, coadministration of iRGD enhanced the uptake of an irinotecan-loaded silicasome carrier that comprises lipid bilayer-coated mesoporous silica nanoparticles (MSNPs); this uptake resulted in enhanced survival and markedly reduced metastasis. Further, ultrastructural imaging of the treated tumors revealed that iRGD coadministration induced a vesicular transport pathway that carried Au-labeled silicacomes from the blood vessel lumen to a perinuclear site within cancer cells. iRGD-mediated enhancement of silicasome uptake was also observed in patient-derived xenografts, commensurate with the level of NRP-1 expression on tumor blood vessels. These results demonstrate that iRGD enhances the efficacy of irinotecan-loaded silicasome-based therapy and may be a suitable adjuvant in nanoparticle-based treatments for PDAC.

Guías clínicas para la alimentación en pacientes con trastorno de la deglución / Clinic guidelines for feeding in-patients with swallowing disorders

Feeding is crucial for children’s development at all ages. For that reason, it is necessary to implement timely and effective diagnosis and treatment for patients that present distress in this activity. Swallowing disorders are associated to multiple pathologies and they are accompanied by serious health conditions. This is the reason why the medical approach of each of these disorders is not considered. Due to this point, it is imperative to make sure an integral management where we should consider diagnosis and treatment for patients with swallowing disorders and general feeding problems. Clinical practice guidelines (gPC) are used as a tool to generate current existing evidence to help professionals and in-patients to solve specific health problems by helping solve diagnosis or therapeutic options for a specific condition. Since 2004, minsal has developed gPC associated to the different pathologies included in ges. Hospitals have worked in generating gPC and health care protocols in order to reduce variability and improve clinical practice.

La alimentación es crucial para el desarrollo de los niños en todas las edades, es por esto, que se hace necesario implementar el diagnóstico y tratamiento, oportuno y efectivo para los pacientes que presenten dificultades en esta actividad. Los trastornos de la deglución, se asocian a múltiples patologías y en general acompañan a graves condiciones de salud, es por esto que, en el abordaje particular de cada una de las enfermedades, en ocasiones no se considera. Dado lo anterior es que se hace imperativo realizar un manejo integral de estos pacientes en el que se debe considerar el diagnóstico y tratamiento de los trastornos de la deglución y de la alimentación en general. Como herramienta para generar y difundir las evidencias existentes en la actualidad sobre algunos temas se ha considerado la generación de guías de práctica clínica (gPC) las que constituyen un conjunto de recomendaciones desarrolladas de forma sistemática para ayudar a profesionales y pacientes en la toma de decisiones sobre problemas específicos de salud, ayudando a seleccionar las opciones diagnósticas o terapéuticas más adecuadas a una condición clínica específica. Desde el año 2004, el minsal ha desarrollado gPC asociadas a las patologías que se han incluido en el régimen de garantías explicitas en salud. Paralelamente en los distintos hospitales del país, públicos y privados se ha trabajado en la generación de gPC y protocolos de atención con el fin de reducir la variabilidad y mejorar la práctica clínica.

Recomendaciones para los cuidados respiratorios del niño y adolescente con enfermedades neuromusculares / Respiratory care for the children and adolescents with neuromuscular diseases

El compromiso del sistema respiratorio repercute directamente en la morbimortalidad de niños y adolescentes con enfermedades neuromusculares (ENM). Un enfoque integral que incluya la aproximación a un diagnostico neurológico específico, evaluación funcional respiratoria, de los trastornos respiratorios de sueño, comorbilidades y afecciones secundarias, permiten orientar a el tipo, grado y pronóstico respiratorio; además de otorgar herramientas objetivas para modificar la historia natural de la enfermedad. Utilizar criterios estrictos de selección, una mirada interdisciplinaria y actividades complementarias de rehabilitación; que incorporen en forma programática la ventilación no invasiva domiciliaria, protocolos de tos asistida y métodos para aumentar la capacidad máxima de insuflación, cambia la evolución, disminuye la morbimortalidad y evita la traqueostomía, en una alta proporción de niños y adolescentes portadores de ENM.