Opportunities for Regulatory Changes to Promote Pediatric Device Innovation in the United States: Joint Recommendations From Pediatric Innovator Roundtables.

Objective: The purpose of this report is to provide insight from pediatric stakeholders with a shared desire to facilitate a revision of the current United States regulatory pathways for the development of pediatric healthcare devices.

Methods: On August 5, 2020, a group of innovators, engineers, professors and clinicians met to discuss challenges and opportunities for the development of new medical devices for pediatric health and the importance of creating a regulatory environment that encourages and accelerates the research and development of such devices. On January 6, 2021, this group joined regulatory experts at a follow-up meeting.

Breathing Signature as Vitality Score Index Created by Exercises of Qigong: Implications of Artificial Intelligence Tools Used in Traditional Chinese Medicine.

Rising concerns about the short- and long-term detrimental consequences of administration of conventional pharmacopeia are fueling the search for alternative, complementary, personalized, and comprehensive approaches to human healthcare. Qigong, a form of Traditional Chinese Medicine, represents a viable alternative approach. Here, we started with the practical, philosophical, and psychological background of Ki (in Japanese) or Qi (in Chinese) and their relationship to Qigong theory and clinical application.

Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a "Watch-and-Wait" Approach to Cancer.

Background: Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cellspecific manner.

Cancer genomic research at the crossroads: realizing the changing genetic landscape as intratumoral spatial and temporal heterogeneity becomes a confounding factor.

The US National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) created the Cancer Genome Atlas (TCGA) Project in 2006. The TCGA's goal was to sequence the genomes of 10,000 tumors to identify common genetic changes among different types of tumors for developing genetic-based treatments. TCGA offered great potential for cancer patients, but in reality has little impact on clinical applications.

Training stem cells for treatment of malignant brain tumors.

The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients.

Therapeutic window, a critical developmental stage for stem cell therapies.

In children, cancers are the deadliest of diseases and second only to accidents as the leading cause of death. The deadliest of the brain cancers are the malignant gliomas. Approximately two-thirds of children can survive less malignant types of brain cancers, however, in ~67% of these survivors recurs under the current regimes of surgery followed by administration of high doses toxic drugs and exposure to high doses of radiation.

A biological global positioning system: considerations for tracking stem cell behaviors in the whole body.

Many recent research studies have proposed stem cell therapy as a treatment for cancer, spinal cord injuries, brain damage, cardiovascular disease, and other conditions. Some of these experimental therapies have been tested in small animals and, in rare cases, in humans. Medical researchers anticipate extensive clinical applications of stem cell therapy in the future.

Topology of the pore-region of a K+ channel revealed by the NMR-derived structures of scorpion toxins.

The architecture of the pore-region of a voltage-gated K+ channel, Kv1.3, was probed using four high affinity scorpion toxins as molecular calipers. We established the structural relatedness of these toxins by solving the structures of kaliotoxin and margatoxin and comparing them with the published structure of charybdotoxin; a homology model of noxiustoxin was then developed.

The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11, encodes the type l K+ channel in T cells.

T lymphocytes exhibit three distinct types of voltage-gated K+ channels, n, n', and l, that are distributed in the T cell lineage according to subset, as well as the cells' activation and developmental status. Type l K+ channels are found sparingly in cytotoxic T cells from normal mice and abundantly in a specific T cell subset (CD4- CD8- Thy1+) from mice with autoimmune disease. Here, we show that the mouse Kv3.

Genomic organization, nucleotide sequence, and cellular distribution of a Shaw-related potassium channel gene, Kv3.3, and mapping of Kv3.3 and Kv3.4 to human chromosomes 19 and 1.

Genomic and cDNA clones encoding a novel Shaw-related potassium channel gene have been isolated from mice and humans. The mouse-Kv3.3 gene encodes a protein of 679 amino acids.

Expression and chromosomal localization of a lymphocyte K+ channel gene.

We recently isolated a family of three closely related mouse K+ channel genes (MK1, MK2, and MK3) with coding regions contained in single uninterrupted exons. Here we have used patch-clamp recordings from Xenopus oocytes injected with mRNA to show that MK3 encodes a channel with biophysical and pharmacological properties indistinguishable from those of voltage-gated type n K+ channels in T cells. In addition, we used the polymerase chain reaction to demonstrate the presence of MK3 mRNA in T cells.

A rabbit model of staphylococcal blepharitis.

Rabbits immunized with cell wall antigens of Staphylococcus aureus developed blepharitis after topical challenge with viable S aureus. The lids of these rabbits were thickened and erythematous. Crusting was found around the lashes, and the lids developed loss of lashes and hair.

The complement system and host defense against Pseudomonas endophthalmitis.

The authors examined the role of the complement system in host defense against Pseudomonas aeruginosa endophthalmitis. Guinea pigs received intravitreal injections of P. aeruginosa, and comparisons were made between bacterial counts from the vitreous of control guinea pigs and experimental guinea pigs that underwent systemic decomplementation with cobra venom factor.

Occurrence of phlyctenules after immunization with ribitol teichoic acid of Staphylococcus aureus.

We immunized rabbits to ribitol teichoic acid (RTA), a component of the cell wall of Staphylococcus aureus, by intravenous injections of RTA-sensitized sheep RBCs. Hemagglutination titers to RTA and corneal phlyctenules developed in these rabbits after topical challenge with viable S aureus, but did not develop in control rabbits immunized with unsensitized sheep RBCs. These results suggest that hypersensitivity to RTA, the major antigenic determinant of S aureus, plays a role in the development of corneal phlyctenules.

Experimental herpesvirus keratitis in the rabbit: topical versus intrastromal infection routes.

Intrastromal and topical routes of infection of rabbit corneas with the HF strain of herpes simplex virus type 1 were compared clinically to determine which route of infection would present the best model of disciform edema and of deep stromal keratitis for our further studies on how the immune response of the infected animals may influence the expression of clinical disease. In addition, virus clearing and persistence of viral antigens as immunologic stimuli were monitored by virologic and electron microscopic immunocytochemical studies. We found topical infection to be preferable to the intrastromal infection route for presenting stromal disease in that it resulted in a higher incidence of epithelial disease with less anterior chamber involvement.

Experimental Klebsiella-induced endophthalmitis in the rabbit.

Klebsiella organisms have been reported in postoperative endophthalmitis. We describe an experimental model of endophthalmitis with anterior segment inflammation over the injection of Klebsiella oxytoca into the rabbit vitreous. Within 24 hours, polymorphonuclear leukocytes were found at the corneal limbus, adjacent to the endothelium, in the iris and ciliary body, throughout the vitreous, and in the optic nerve.