NfL concentration in CSF is a quantitative marker of the rate of neurodegeneration in aging and Huntington's disease: a semi-mechanistic model-based analysis.

The concentrations of neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and plasma have become key biomarkers of many neurodegenerative diseases, including Huntington's Disease (HD). However, the relationship between the dynamics of NfL concentrations in CSF and the time-course of neurodegeneration (whole brain atrophy) has not yet been described in a quantitative and mechanistic manner. Here, we present a novel semi-mechanistic model, which postulates that the amount of NfL entering the CSF corresponds to the amount of NfL released from damaged neurons, whose degeneration results in a decrease in brain volume. In mathematical terms, the model expresses the NfL concentration in CSF in terms of the NfL concentration in brain tissue, the rate of change of whole brain volume and the CSF flow rate. To test our model, we used a non-linear mixed effects approach to analyze NfL and brain volume data from the HD-CSF study, a 24-month prospective study of individuals with premanifest HD, manifest HD and healthy controls. The time-course of whole brain volume, obtained from MRI, was represented empirically by a 2nd order polynomial, from which its rate of change was computed. CSF flow rates in healthy and HD populations were taken from recent literature data. By estimating the NfL concentration in brain tissue, the model successfully described the time-course of the NfL concentration in CSF in both HD subjects and healthy controls. Furthermore, the model-derived estimate of NfL concentration in brain agreed well with recent direct experimental measurements. The consistency of our model with the NfL and brain volume data suggests that the NfL concentration in CSF reflects the rate, rather than the extent, of neurodegeneration and that the increase in NfL concentration over time is a measure of the accelerating rate of neurodegeneration associated with aging and HD. For HD subjects, the degree of acceleration was found to increase markedly with the number of CAG repeats on their HTT gene. The application of our semi-mechanistic NfL model to other neurodegenerative diseases is discussed.

Establishment and Validation of a New Co-Culture for the Evaluation of the Permeability through the Blood-Brain Barrier in Patients with Glioblastoma.

Currently, the mechanisms involved in drug access to the central nervous system (CNS) are not completely elucidated, and research efforts to understand the behaviour of the therapeutic agents to access the blood-brain barrier continue with the utmost importance. The aim of this work was the creation and validation of a new in vitro model capable of predicting the in vivo permeability across the blood-brain barrier in the presence of glioblastoma. The selected in vitro method was a cell co-culture model of epithelial cell lines (MDCK and MDCK-MDR1) with a glioblastoma cell line (U87-MG). Several drugs were tested (letrozole, gemcitabine, methotrexate and ganciclovir). Comparison of the proposed in vitro model, MDCK and MDCK-MDR1 co-cultured with U87-MG, and in vivo studies showed a great predictability for each cell line, with R2 values of 0.8917 and 0.8296, respectively. Therefore, both cells lines (MDCK and MDCK-MDR1) are valid for predicting the access of drugs to the CNS in the presence of glioblastoma.

Impacts of COVID-19 on the early care and education sector in California: Variations across program types.

The COVID-19 crisis has overwhelmed and weakened the United States early care and education (ECE) sector, jeopardizing a system that was already precariously situated atop a weak foundation. While multiple national- and state-level studies have highlighted the overwhelming impacts of the pandemic on the ECE sector, little has been reported about how much variation in impacts exists, and in what forms, within the ECE sector. Based on a statewide survey of 953 licensed care providers in California conducted in June 2020, this paper examines the impact of COVID-19 experienced by ECE providers, focusing on the variations between centers and family child care homes (FCCs) and among center-based programs. Results indicate that the challenges programs face differ greatly depending on program type and funding source. Compared to center-based programs, FCCs fared worse in most measures of economic hardship that directly impact individual providers with medium to large effect sizes. Centers were more likely than FCCs to struggle with reduced attendance and changes in program operations by medium to large effect sizes and report staffing challenges by small to medium effect sizes. Among the center-based programs, subsidized programs holding contracts with Head Start or the California Department of Education (such as state preschool programs) were more stable and better able to financially support their staff during the pandemic, with effect sizes ranging from medium to large. Centers receiving government subsidies in the form of vouchers were more likely to be negatively impacted by the pandemic compared to unsubsidized centers and Head Start and state-contracted centers. Implications for future research and policy are discussed in the context of addressing the complex delivery system of ECE services and supporting outcomes that are effective and equitable for children, families, and the ECE workforce.

Knowledge, Attitudes, and Sources of Information on Vaccines in Spanish Nursing Students: A Cross-Sectional Study.

Health professionals are the most influential and main sources of information about vaccines for the general population, as they are regarded as role models by patients and society. The objective of the present study was to determine the knowledge and attitudes of a group of university Nursing students about vaccines, as well as their sources of information and their education needs. A cross-sectional study was performed through a questionnaire (55 items) provided to Nursing students at two Spanish universities. A total of 1122 students participated in the study. The mean score obtained for knowledge about vaccines was 44.6 ± 4.3, and for attitudes towards vaccines, it was 37.2 ± 3.9. Hepatitis B (94.7%) and the Flu (89%) are the two main vaccines they should receive as health workers. The main source of information was the family environment (65.6%). Most of them considered that post-graduate education about vaccines should be provided by academic entities (universities, 62.7%). Among the health professionals, Nurses (85.5%) must be better educated and trained on the subject of vaccines. It is therefore necessary to delve into and complete the nurses' training on vaccines, to educate them about the risks at the individual level, and their decisive role as promoters of the vaccination strategy for the general population. Universities must become the leaders in vaccine education and training.

La suspensión de la Diálisis en pacientes con Insuficiencia Renal Crónica Avanzada: ¿Qué opinan los enfermos? / Withdrawing dialysis in End-Stage Renal Disease: ¿What do patients think about it?

El proceso de voluntades anticipadas permite a los pacientes dar a conocer sus preferencias. Método: estudio cualitativo de subgrupos homogéneos con pacientes con enfermedad renal crónica en programa de diálisis a través de entrevistas semiestructuradas, con el objetico de conocer su deseo de participar en la toma de decisiones sanitarias, en particular las relacionadas con el final de la vida. Resultados: de mayo a diciembre de 2012 se entrevistaron a catorce pacientes, con una mediana de edad de 66 años. Creen que reciben una información adecuada, pero reconocen que no se les habla sobre el final de la vida o la retirada de diálisis. Creen que los médicos no hablan de ello porque están centrados en otras cuestiones y no quieren entristecerles. Quieren participar en la toma de decisiones y expresar sus preferencias. En caso de deterioro neurológico severo preferirían suspender la diálisis y recibir tratamiento para no tener dolor, en su casa si es posible. Sería conveniente integrar los cuidados paliativos en la asistencia de los pacientes en diálisis (AU)

Advance Care Planning (ACP) helps communicate patients’ end-of-life care, particularly for older patients. Method: prospective qualitative study carried out on selected ESRD patients from a dialysis unit. The aim was to determine what was most important to the patient, if they wanted to participate in decision-making process and what degree of functional impairment they would consider intolerable. Two semi-structured interviews with each patient were performed, including their relatives. Results: from May to December 2012 fourteen patients with an average age of 66 years were interviewed. They believe that the information process is adecuate, but there is no information about the plan of care if a trasplant is not a real option. They would like to participate in decisions concerning their care and end-of-life. They would want to keep on with dialysis treatment while their quality of life continues to be acceptable for them. Respecting end-of-life care, dying without pain and to be cared for at home are the most important points for them. Patients think that doctors don ́t speak to them about end-of-life because they are focused on other aspects of care. Conclusion: although there are great opportunities to talk with ESRD patients about end-of-life care this is often not done. In cases with severe cognitive impairment they would prefer to withdraw dialysis. Then they wish to receive care at home to relieve suffering or pain. The best way to achieve this is by integrating palliative care into dialysis units (AU)