The perils of boarding: A call to achieve parity in the delivery of acute psychiatric services for children with COVID-19.

Boarding across pediatric healthcare systems is on the rise during the pandemic. Children with positive COVID-19 test results awaiting psychiatric placements in the emergency department or medical unit settings are at increased risk for decompensation with unmet psychiatric needs during a time of crisis marked by vulnerability. There is scant literature unveiling best practices on delivery of care for these patients to achieve acute crisis stabilization. Recent studies have uncovered substantial increases in mental health disorders among children during the pandemic compared to previous incidence and prevalence rates prior to the pandemic. From the published literature, two healthcare systems have initiated long-term planning, development, and implementation of biodome psychiatric units for patients with COVID-19 in need of acute crisis stabilization services. We sampled 100 acute inpatient child and adolescent psychiatric programs to discern their post-COVID positive clearance policies for admission. Findings were mixed among days of quarantine required, symptomology, covid-designated spaces vs. self-isolated rooms for psychiatric treatment, number of COVID negative retests, and additional considerations. We also review a range of considerations and recommendations for clinical practice and the health system in achieving parity in mental health care for these patients which in turn could contribute towards mitigating the rising global mental health crisis. Furthermore, increasing access to acute psychiatric services for these patients will also contribute towards the larger goal of the World Health Organization, Sustainable Developmental Goals of the United Nations, and Healthy People 2030 in increasing accessibility, quality and equity of mental health care for individuals on both global and national frontiers.

Homeless in the hospital: A call to strengthen multidisciplinary care for children awaiting out-of-home and psychiatric placements.

Increasingly more school-age and adolescent children continue to await psychiatric or out-of-home placements across pediatric healthcare systems. These children comprise the growing overstay pediatric population. The medical, developmental, socioemotional, behavioral and academic needs of these patients are complex and diverse. The uncertainty of waiting times for placement further continues. This growing pediatric issue emphasizes the importance of mobilizing a myriad of resources across healthcare and community contexts to support these patients during this precarious time. The reality is that there is a significant scarcity of placement resources which contributes to extended waiting times for placement. This contemporary issue brings child development, ethical and moral considerations, and healthcare operations to the forefront. We discuss a myriad of dimensions surrounding this growing issue from our clinical practice. We present a wealth of recommendations in working through each of these dimensions through a multi-systems approach that include development of individualized care plan, access to consistent psychiatric services, and implementing short-term and long-term goals pertaining to treatment and placement. We also review our clinical practices that have supported these patients on a continuum at our healthcare institution which integrate our recommendations and also involve an open line of communication with established community partners involved in the care of these children. Furthermore, we propose suggestions from an operational perspective on developing a comprehensive, multidisciplinary care model for this fragile and oftentimes neglected patient population across the healthcare system as the basis to achieve equity and translational impact in the quality and delivery of healthcare care services across pediatric healthcare systems.

Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis.

A peptide from the P0 acidic ribosomal protein (pP0) of ticks conjugated to keyhole limpet hemocyanin from Megathura crenulata has shown to be effective against different tick species when used in host vaccination. Turning this peptide into a commercial anti-tick vaccine will depend on finding the appropriate, technically and economically feasible way to present it to the host immune system. Two conjugates (p64K-Cys1pP0 and p64K-ßAla1pP0) were synthesized using the p64K carrier protein from Neisseria meningitidis produced in Escherichia coli, the same cross-linking reagent, and two analogues of pP0. The SDS-PAGE analysis of p64K-Cys1pP0 showed a heterogeneous conjugate compared to p64K-ßAla1pP0 that was detected as a protein band at 91kDa. The pP0/p64K ratio determined by MALDI-MS for p64K-Cys1pP0 ranged from 1 to 8, being 3-5 the predominant ratio, while in the case of p64K-ßAla1pP0 this ratio was 5-7. Cys1pP0 was partially linked to 35 out of 39 Lys residues and the N-terminal end, while ßAla1pP0 was mostly linked to the six free cysteine residues, to the N-terminal end, and, in a lesser extent, to Lys residues. The assignment of the conjugation sites and side reactions were based on the identification of type 2 peptides. Rabbit immunizations showed the best anti-pP0 titers and the highest efficacy against Rhipicephalus sanguineus ticks when the p64K-Cys1pP0 was used as vaccine antigen. The presence of high molecular mass aggregates observed in the SDS-PAGE analysis of p64K-Cys1pP0 could be responsible for a better immune response against pP0 and consequently for its better efficacy as an anti-tick vaccine. Graphical abstract.

BRCA1 transcriptionally regulates genes involved in breast tumorigenesis.

Loss of function of BRCA1 caused by inherited mutation and tissue-specific somatic mutation leads to breast and ovarian cancer. Nearly all BRCA1 germ-line mutations involve truncation or loss of the C-terminal BRCT transcriptional activation domain, suggesting that transcriptional regulation is a critical function of the wild-type gene. The purpose of this project was to determine whether there is a link between the role of BRCA1 in transcriptional regulation and its role in tumor suppression. We developed a cell line (in which BRCA1 can be induced) and used microarray analysis to compare transcription profiles of epithelial cells with low endogenous levels of BRCA1 vs. transcription profiles of cells with 2-4-fold higher induced levels of expression of BRCA1. At these levels of expression, BRCA1 did not induce apoptosis. Undirected cluster analysis of six paired experiments revealed 373 genes, the expression of which was altered significantly and consistently by BRCA1 induction. Expression of 62 genes was altered more than 2-fold. BRCA1-regulated genes associated with breast tumorigenesis included the estrogen-responsive genes MYC and cyclin D1, which are overexpressed in many breast tumors; STAT1 and JAK1, key components of the cytokine signal transduction pathway; the extracellular matrix protein laminin 3A; ID4, an inhibitor of DNA-binding transcriptional activators, which in turn negatively regulates BRCA1 expression; and the prohormone stanniocalcin, expression of which is lost in breast tumor cells. Coordinated expression of BRCA1 with ID4 and with stanniocalcin was confirmed in primary breast and ovarian tumors.