Pregnant mice were given to daily dose of 0, 0.18, or 9.0 mg Diazinon per kilogram body weight throughout gestation. Mothers of all dose groups gave birth to viable, overtly normal offspring. However, pups born to mothers receiving the higher dose of the organophosphate grew significantly slower than controls and remained significantly smaller at 1 month of age. Offspring of mothers receiving the lower dose apparently were unaffected, but systematic behavioral testing revealed subtle deviations from normal developmental ontogeny as shown by significant delays in the appearance of the contact placing reflex and of sexual maturity (descent of testes or vaginal opening). Mature offspring of mothers exposed to either dose of the pesticle displayed impaired endurance and coordination on rod cling and inclined plane tests of neuromuscular function. Offspring from the 9.0 mg/kg group, in addition, had slower running speeds in a Lashley III maze and less endurance in a swimming test. Brains obtained after sacrifice at 101 days of age revealed neuropathology in the forebrains of offspring born of mothers exposed to the higher dose. Despite functional impairments in offspring from the lower dose group, no corresponding brain pathology was observed by examination under the light microscope.
Multiple myeloma (MM) is a heterogeneous disease with high-risk patients progressing rapidly despite treatment. Various definitions of high-risk MM are used and we reported that gene expression profile (GEP)-defined high risk was a major predictor of relapse. In spite of our best efforts, the majority of GEP70 high-risk patients relapse and we have noted higher relapse rates during drug-free intervals. This prompted us to explore the concept of less intense drug dosing with shorter intervals between courses with the aim of preventing inter-course relapse. Here we report the outcome of the Total Therapy 5 trial, where this concept was tested. This regimen effectively reduced early mortality and relapse but failed to improve progression-free survival and overall survival due to relapse early during maintenance.
Background Arkansas is a rural state of 3 million people. It is ranked fifth for poverty nationally. 1 The first case of COVID‐19 in Arkansas occurred on March 11, 2020. Since then, approximately 8% of all Arkansans have tested positive. Given the resource limitations of Arkansas, COVID‐19 convalescent plasma (CCP) was explored as a potentially life‐saving, therapeutic option. Therefore, the Arkansas Initiative for Convalescent Plasma was developed to ensure that every Arkansan has access to this therapy. Study Design and Method This brief report describes the statewide collaborative response from hospitals, blood collectors, and the Arkansas Department of Health (ADH) to ensure that COVID‐19 convalescent plasma was available in a resource‐limited state. Results Early contact tracing by ADH identified individuals who had come into contact with “patient zero” in early March. Within the first week, 32 patients tested positive for COVID‐19. The first set of CCP collections occurred on April 9, 2020. Donors had to be triaged carefully in the initial period, as many had recently resolved their symptoms. From our first collections, with appropriate resource and inventory management, we collected sufficient CCP to provide the requested number of units for every patient treated with CCP in Arkansas. Conclusions The Arkansas Initiative, a statewide effort to ensure CCP for every patient in a resource‐limited state, required careful coordination among key players. Collaboration and resource management was crucial to meet the demand of CCP products and potentially save lives. This article is protected by copyright. All rights reserved.
Acute administration of Aroclor-1254 (500 mg/kg) or 3,4,5,3',4',5'-hexabromobiphenyl (HBB) (2-6 mg/kg) IP, profoundly inhibited the plaque forming response to subsequent challenge with sheep erythrocytes in Ah locus positive (C57Bl/6N or B6C3F1N) mice. These studies showed: the immunotoxicity results paralleled enzyme induction results insofar as HBB was approximately 100 times more potent than Aroclor 1254; neither Aroclor nor HBB treatment caused significant induction in the Ah locus negative DBA/2N mice; when B6C3F1 mice were challenged with sheep red blood cells (SRBC) 6 or 16 weeks post Aroclor 1254 treatment, substantial recovery of a PFC response was observed; when these compounds were administered to older (76-week-old) (B6C3F1 mice, severe depression of a PFC response was observed. In contrast to its profound depression of a PFC response, Aroclor-1254 (up to 1250 mg/kg) caused slight increases in lymphocyte proliferation induced by either T or B cell mitogens. A single 500 mg/kg dose of Aroclor-1254 also suppressed the ability of recipient B6C3F1 animals to reject a challenge with either the syngenic fibrosarcoma (PYB6) or the gram negative pathogen (Listeria monocytogenes).
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