Modeling, synthesis and cell-based evaluation of pyridine-substituted analogs of CD3254 and fluorinated analogs of CBt-PMN as novel therapeutics.

Six pyridine analogs of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid-or CD3254 (11)-in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzo[d][1,2,3]triazole-5-carboxylic acid (CBt-PMN or 23) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), an FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Treatment with 1 often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay.

The Effect of Open and Closed Oocyte Vitrification Systems on Embryo Development: A Systematic Review and Network Meta-Analysis.

: Open and closed vitrification systems are commonly employed in oocyte cryopreservation; however, there is limited evidence regarding a comparison of their separate impact on oocyte competence. This study uniquely brings to the literature, data on the effect of open versus closed vitrification systems on laboratory and clinical outcomes, and the effect of cooling and warming rates. : A systematic search of the literature was performed using the databases PubMed/MEDLINE and the Cochrane Central Library, limited to articles published in English up to January 2023.

Remote IVF: a clinical and laboratory guide to performing remote oocyte retrievals.

The aim of this guide is to describe different scenarios when remote IVF would be needed, considerations around how to plan for the procedure, proper equipment in the procedure room, and proper transportation of oocytes from the procedure room. There are two different scenarios for remote IVF: (1) IVF clinics designed knowing the embryology laboratory is nonadjacent and (2) IVF clinics that routinely provide care to patients in their clinic and want to provide care to those who are ineligible for a retrieval under anesthesia in an outpatient facility. This guide will focus on both scenarios.

Viral infection and allergy status impact severity of asthma symptoms in children with asthma exacerbations.

Background: Although viral infection is known to be associated with asthma exacerbations, prior research has not identified reliable predictors of acute symptom severity in virus-related asthma exacerbations (VRAEs).

Objective: To determine the effect of asthma control and viral infection on the severity of current illness and evaluate biomarkers related to acute symptoms during asthma exacerbations.

Methods: We prospectively enrolled 120 children with physician-diagnosed asthma and current wheezing who presented to Arkansas Children's Hospital emergency department.

Experimental Bovine Spongiform Encephalopathy in Squirrel Monkeys: The Same Complex Proteinopathy Appearing after Very Different Incubation Times.

Incubation periods in humans infected with transmissible spongiform encephalopathy (TSE) agents can exceed 50 years. In humans infected with bovine spongiform encephalopathy (BSE) agents, the effects of a "species barrier," often observed when TSE infections are transmitted from one species to another, would be expected to increase incubation periods compared with transmissions of same infectious agents within the same species. As part of a long-term study investigating the susceptibility to BSE of cell cultures used to produce vaccines, we inoculated squirrel monkeys ( sp.

Cryopreservation Does Not Affect the Clinical Pregnancy Rate of Blastocysts Derived from Vitrified Oocytes.

Vitrified, or "frozen", donor eggs can either be fertilized and cultured for fresh transfer (group 1), or fertilized and cryopreserved for transfer in a "frozen embryo transfer" cycle (group 2). This study compared the pregnancy rates between the two groups. Frozen donor egg cycles (N = 1213) were analyzed at the World Egg Bank.

The ART of cryopreservation and its changing landscape.

The purpose of this review is to educate the reader on the role that cryopreservation has played and continues to play in the ever-evolving field of assisted reproductive technologies, specifically in clinical human fertility treatment. We discuss the science behind the cryopreservation methods and investigated some of the major considerations that any clinic or cryobank faces in terms of risks and liabilities, physical challenges that accompany the constantly growing collection of cryopreserved specimens, and what this means on the ethical and legal front. Finally, we take a glimpse in the future to explore what may be on the horizon for the preservation of gametes and reproductive tissues.

Behavioral, Physiological, and Neural Signatures of Surprise during Naturalistic Sports Viewing.

Surprise signals a discrepancy between past and current beliefs. It is theorized to be linked to affective experiences, the creation of particularly resilient memories, and segmentation of the flow of experience into discrete perceived events. However, the ability to precisely measure naturalistic surprise has remained elusive.

Cryopreservation and IVF in the time of Covid-19: what is the best good tissue practice (GTP)?

Examine good tissue practices as relates to in vitro fertilization, biopsying, and vitrificationto compare current knowledge of ova, sperm, and embryos as vectors for disease transmission as it relates to our current knowledge regarding the SARS-CoV-2 virus.Unknown risks relating to the SARS-CoV-2 virus and sperm, ova, and embryos necessitate a reexamining of how human IVF is performed. Over the last decade, improvements in cryosurvival and live birth outcomes have been associated with zona pellucida breaching procedures (e.

Cryostorage tank failures: temperature and volume loss over time after induced failure by removal of insulative vacuum.

Purpose: To determine liquid nitrogen evaporation rates of intact liquid nitrogen storage tanks and tanks with their vacuum removed.

Methods: Donated storage tank performance (LN2 evaporation) was evaluated before and after induced vacuum failure. Vacuum of each tank was removed by drilling through the vacuum port.

Reproductive Tissue Storage: Quality Control and Management/Inventory Software.

The recent failure of two liquid nitrogen storage tanks at two separate facilities in the United States has highlighted the need to reexamine our approach to how reproductive laboratories handle the storage of tissue. If we wish to truly understand how we can increase the security and safety of stored reproductive tissue, we really need to understand how often these events (tank failure) occur and what are the ultimate causes of these failures. Are there design flaws in the storage tanks or are these really failures in protocols and following protocols? Unfortunately, because these cases often involve serious litigation, most do not want to or are forbidden to talk about these failures and so we have little data to base recommendations on.

ER-associated degradation regulates Alzheimer's amyloid pathology and memory function by modulating γ-secretase activity.

Endoplasmic-reticulum-associated degradation (ERAD) is an important protein quality control system which maintains protein homeostasis. Constituents of the ERAD complex and its role in neurodegeneration are not yet fully understood. Here, using proteomic and FRET analyses, we demonstrate that the ER protein membralin is an ERAD component, which mediates degradation of ER luminal and membrane substrates.

Patient and tissue identification in the assisted reproductive technology laboratory.

Several high-profile cases involving in vitro fertilization have recently received considerable media attention and highlight the importance of assuring patient and tissue identification. Within the assisted reproductive technology (ART) laboratory, there are many steps where wrong patient or tissue identity could have drastic results. Erroneous identity can result in tragic consequences for the patient, the laboratory, and for those working in the program as a whole.

Candidate cell substrates, vaccine production, and transmissible spongiform encephalopathies.

Transmissible spongiform encephalopathy (TSE) agents have contaminated human tissue-derived medical products, human blood components, and animal vaccines. The objective of this study was to determine the potential susceptibility to infection of 5 cell lines used or proposed for manufacture of biological products, as well as other lines. Cell lines were exposed to the infectious agents of sporadic and variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (BSE).

Squirrel monkeys (Saimiri sciureus) infected with the agent of bovine spongiform encephalopathy develop tau pathology.

Squirrel monkeys (Saimiri sciureus) were infected experimentally with the agent of classical bovine spongiform encephalopathy (BSE). Two to four years later, six of the monkeys developed alterations in interactive behaviour and cognition and other neurological signs typical of transmissible spongiform encephalopathy (TSE). At necropsy examination, the brains from all of the monkeys showed pathological changes similar to those described in variant Creutzfeldt-Jakob disease (vCJD) of man, except that the squirrel monkey brains contained no PrP-amyloid plaques typical of that disease.

National collection of embryo morphology data into Society for Assisted Reproductive Technology Clinic Outcomes Reporting System: associations among day 3 cell number, fragmentation and blastomere asymmetry, and live birth rate.

Objective: To evaluate the validity of collecting day 3 embryo morphology variables into the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS).

Design: Retrospective.

Setting: National database-SART CORS.

Standardization of grading embryo morphology.

Standardization of morphologic assessment for an embryo grading system was developed and is being implemented by the Society for Assisted Reproductive Technology (SART). A recent European consensus conference of embryologists from Europe and America is working toward adopting an embryo classification system modeled similarly to that of SART that, if adopted, would produce a de facto international standard to aid cross-border collaboration.

Standardization of grading embryo morphology.

Standardization of morphological assessment for embryo grading system was developed and is being implemented by the Society for Assisted Reproductive Technology (SART). A recent European consensus conference of embryologists from Europe and America is working toward adopting an embryo classification system modeled similarly to that of SART which, if adopted, would produce a de facto international standard to aid cross border collaboration.

Storage of cryopreserved reproductive tissues: evidence that cross-contamination of infectious agents is a negligible risk.

A misconception in the field of reproductive medicine is that there is a significant risk of cross-contamination during gamete or embryo cryostorage. This article is a review of the available literature on animal models and human IVF and it suggests otherwise. There is a negligible risk of cross-contamination in IVF working conditions.

Prion proteins in subpopulations of white blood cells from patients with sporadic Creutzfeldt-Jakob disease.

Recent cases of prion transmission in humans following transfusions using blood donated by patients with asymptomatic variant Creutzfeldt-Jakob disease (CJD) implicate the presence of prion infectivity in peripheral blood. In this study, we examined the levels of the normal, cellular prion protein (PrPC), and the disease-causing isoform (PrPSc) in subpopulations of circulating white blood cells (WBCs) from patients with sporadic (s) CJD, age-matched neurological controls and healthy donors. Though widely distributed, the highest levels of PrPC were found in a subpopulation of T lymphocytes: approximately 12,000 PrPC molecules were found per CD4+CD45RA-CD62L- effector memory T helper cell.

Optimization of equipment and methodology for whole body activity retention measurements in children undergoing targeted radionuclide therapy.

Accurate measurements of whole-body activity retention of patients during radionuclide therapy are essential for two reasons: First, they enable the correct radiation protection advice to be given and second, they permit the accurate determination of the absorbed whole-body dose delivered during therapy. This, in turn, allows treatment planning to be carried out for future radionuclide therapy on an individual patient basis, and also enables the investigation of the potential correlation of absorbed dose with treatment outcome in groups of patients. There are significant difficulties associated with taking whole-body retention measurements of children, especially when they are very young and/or unwell.

Computerized morphometric analysis of pathological prion protein deposition in scrapie-infected hamster brain.

Transmissible spongiform encephalopathies (TSEs or prion diseases) are characterized by a constellation of typical though variable pathological changes in the brain. Deposition of disease-associated abnormal prion protein (PrP(Sc)) is the pathological feature of TSEs most consistent and accessible for quantification. However, the evaluation of PrP(Sc) deposits detected by immunohistochemical techniques has been traditionally based on arbitrarily assigned semiquantitative scores.

Estimated radiation dose to breast feeding infant following maternal administration of 57Co labelled to vitamin B12.

Administration of a radiopharmaceutical may result in a radiation dose to an infant due to ingestion of the radiopharmaceutical secreted in the breast milk. Following a maternal administration of Co labelled to vitamin B12 (cyanocobalamin) as part of a Schilling test an estimate of the absorbed dose to a breast feeding infant was calculated. Milk samples were collected from every feed in the first 24 h, and at approximately 48 and 72 h post-administration.

Evidence that the hexose-to-sucrose ratio does not control the switch to storage product accumulation in oilseeds: analysis of tobacco seed development and effects of overexpressing apoplastic invertase.

Wild-type tobacco (Nicotiana tabacum L.) seed development was characterized with respect to architecture and carbohydrate metabolism. Tobacco seeds accumulate oil and protein in the embryo, cellular endosperm and inner layer of the seed coat.