Notes

"Protein" will no longer implies just what it accustomed to.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak initiated the global COVID-19 pandemic resulting in 42.9 million confirmed infections and >1.1 million deaths worldwide as of October 26, 2020. Remdesivir is a broad-spectrum nucleotide prodrug shown to be effective against enzootic coronaviruses. The pharmacokinetics (PK) of remdesivir in plasma have recently been described. However, the distribution of its active metabolite nucleoside triphosphate (NTP) to the site of pulmonary infection is unknown in humans. Our objective was to use existing in vivo mouse PK data for remdesivir and its metabolites to develop a mechanism-based model to allometrically scale and simulate the human PK of remdesivir in plasma and NTP in lung homogenate. Remdesivir and GS-441524 concentrations in plasma and total phosphorylated nucleoside concentrations in lung homogenate from Ces1c-/- mice administered 25 or 50 mg/kg of remdesivir subcutaneously were simultaneously fit to estimate PK parameters. The mouse PK model was allometrically scaled to predict human PK parameters to simulate the clinically recommended 200 mg loading dose followed by 100 mg daily maintenance doses administered as 30-minute intravenous infusions. Simulations of unbound remdesivir concentrations in human plasma were below 2.48 μM, the 90% maximal inhibitory concentration for SARS-CoV-2 inhibition in vitro. Simulations of NTP in lung were below high efficacy in vitro thresholds. We have identified a need for alternative dosing strategies to achieve more efficacious concentrations of NTP in human lung, perhaps by reformulating remdesivir for direct pulmonary delivery.
Maternal diet quality during pregnancy has been linked to offspring's physical and mental health outcomes across the lifespan. However, few studies have examined its association with subsequent offspring's anxiety and depression issues.

The objective of the study was to examine the relationship between maternal prenatal dietary patterns and offspring's anxiety and depression symptoms from 3 to 8 years.

We used data from 1242 children enrolled in the French EDEN (Etude des déterminants pré- et postnatals précoces du développement et de la santé de l'enfant) birth cohort. Maternal third trimester dietary patterns-namely, "Healthy" (i.e., high intake in fruit, vegetables, fish, and whole-grain cereals) and "Western" (i.e., high intake in processed and snacking foods) patterns-were evaluated using a validated qualitative FFQ. Children's anxiety and depression symptoms (i.e., fears, worries, misery, nervousness, and somatic symptoms) were assessed by mothers using the Strengths and Difficulties Questionnaireiation with subsequent offspring anxiety and depression symptoms in aiming to later inform prevention strategies focusing on pregnancy.
High maternal prenatal adherence to a Healthy dietary pattern was negatively related to anxiety and depression symptoms in children. As maternal diet is a key lifestyle factor, further research should investigate its association with subsequent offspring anxiety and depression symptoms in aiming to later inform prevention strategies focusing on pregnancy.La enfermedad grave por coronavirus 2019 (COVID-19) está causada por el Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) y predispone a complicaciones trombóticas. En esta revisión se aborda de manera práctica la estrecha relación entre la tromboembolia venosa y la COVID-19, enfatizando aspectos epidemiológicos, factores de riesgo y tromboprofilaxis, así como potenciales opciones de anticoagulación. Actualmente la evidencia científica es muy escasa, pero día a día seguimos aprendiendo, estando atentos a cambios novedosos y dinámicos en esta enfermedad infecciosa e inmunotrombótica emergente.Objectives The aim of this study is to report the results of a second cycle audit of the use of subcutaneous levetiracetam (Keppra®) and an updated literature review of management of seizures in palliative care patients. Methods A comprehensive literature review on the use of subcutaneous levetiracetam performed in 2016 was updated. A retrospective audit of the use of subcutaneous levetiracetam for inpatients at Sir Michael Sobell House Hospice during the period of 2019-2020 was performed. Ethical approval was not required and was therefore not sought. Results We report an additional 66 cases identified through an updated literature review and our audit. Fourteen articles were identified from the literature review, reporting a total of 120 cases where subcutaneous levetiracetam was administered. We report 19 further cases of subcutaneous levetiracetam administration between April 2019 and April 2020. Doses ranged from 500 mg to 4000 mg daily. Doses above 2000 mg were administered using a T60 syringe driver. The oral-to-subcutaneous conversion ratio was 11 in all but one case where the dose had to be reduced to fit a T34 syringe driver, after which the T60s were purchased. Levetiracetam was not mixed with other medications, but administered alone using water as the diluent for injection. Where necessary, the dose was appropriately adjusted for renal function. No site reactions were reported. Conclusions Combined analysis of the 139 cases of subcutaneous levetiracetam administration suggests that this treatment continues to have a role in management of seizures at the end of life. Clinical outcomes suggest that therapeutic levels may be achieved, although there are only very limited data available with a few cases worldwide to support this. Randomized controlled trials are urgently needed to establish the efficacy and tolerability of subcutaneous levetiracetam administration.Metastasis is a major cause of morbidity and mortality in cancer patients. However, the molecular and cellular mechanisms underlying the ability of cancer cells to metastasize remain relatively poorly understood. Among all solid tumors, small cell lung cancer (SCLC) has remarkable metastatic proclivity, with a majority of patients diagnosed with metastatic disease. Our understanding of SCLC metastasis has been hampered for many years by the paucity of material from primary tumors and metastases, as well as the lack of faithful pre-clinical models. Here, we review recent advances that are helping circumvent these limitations. These advances include methods that employ circulating tumor cells from the blood of SCLC patients and the development of diverse genetically engineered mouse models of metastatic SCLC. SGI-1776 New insights into the cellular mechanisms of SCLC metastasis include observations of cell fate changes associated with increased metastatic ability. Ongoing studies on cell migration and organ tropism promise to expand our understanding of SCLC metastasis.
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