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Applicator personnel were monitored during aerial and ground applications of EPN to cotton in Mississippi and Arizona. Respiratory exposure based on an 8-hr workday averaged 11 μg for pilots, 15 μg for loaders, and 39 μg for ground applicators. Respiratory exposure of flagmen, monitored during a complete application cycle, averaged 317 μg/8 hr. Mean 8-hr dermal exposures were 2.1 mg for pilots, 6.3 mg for loaders, 117.7 mg for flagmen, and 7.5 mg for ground applicators. The levels of exposure were affected by route of exposure, body region, method of application, job function, attitude and experience, duration of exposure, weather conditions, and accidents. Recommendations are made to reduce the exposure of pilots, loaders, and ground applicators by modification of procedures and use of personal protective equipment. Because flagmen had the greatest exposure, a recommendation is made to substitute their function with fixed landmarks; if this is not possible, flagmen must wear the proper protective equipment. [ABSTRACT FROM AUTHOR]

Intraperitoneal injection of [4-Cl, 2-C] p-chlorophenylalanine (pCPA) (300 mg/kg) in rats revealed absence of chlorine in pure hepatic phenylalanine hydroxyase, while the carbon label appeared as 1-4 moles/mole of [C]tyrosine in the inactivated phenylalanine and cerebral tryptophan-5-hydroxylase. Crystalline muscle aldolase and tyrosine hydroxylase also revealed the presence of [2-C]tyrosine from [2-C] pCPA without inactivating these enzymes. Injection of L-[(U)-C] tyrosine led to its incorporation into the above enzymes, but to a different degree without altering the enzyme activity. Repeated injections of p-chlorophenylacetic acid had no effect on phenylalanine or tryptophan-hydroxylase. Administration of pCPA did not change the levels of cerebral biopterins. Reexamination of the effect of cycloheximide on reversing enzymic inactivation by pCPA failed to confirm our earlier observation. [ABSTRACT FROM AUTHOR]

Repeated intraventricular injections of 2,4-diamino-6-hydroxypyrimidine (DAOPyr), inhibitor of d-erythro-q-dihydroneopterin triphosphate synthetase, inhibited q-BH synthesis from GTP, markedly increased accumulation of 2-amino-4-hydroxy-5(or-6)-formamido-6-triphosphoribosylaminopyrimidine (FPyd-P) and brought about a 60% decrease in the in vivo of reduced biopterin (BH and BH) pool in the brain. Nevertheless, there was no effect on the rate of hydroxylation of l-tryptophan or on the 5-hydroxytryptamine level in rat brain. These data emphasized the significance of the rate of hydrogen transfer and the limitation of the concept of 'unsaturation' (i.e., the absolute amount of the carrier pterin molecule) for the synthesis of neurotransmitters in vivo. [ABSTRACT FROM AUTHOR]

A significant amount of money ($1.76B annually in the United States) is spent on workforce development programs, while there is limited research on the effectiveness of workforce development programs in meeting their program objectives and assisting program participants in attaining employment. This study evaluated the New Choices Program, a workforce development program offered by PA Women Work, to help its clients obtain employment and overcome personal and professional barriers. The program has historically been offered in a 30-hour in person format but was forced to be modified to a 10-hour virtual program when the COVID-19 pandemic restrictions began. This program evaluation included a comparative analysis of the perceptions of participants in the 30-hour in person program and the 10-hour virtual program. It was found that participants in both the 30-hour in person program and 10-hour virtual program perceived the program positively, experienced an increase in self-confidence and belonging, which led to either obtaining employment or being better prepared for the job search process. The data will help inform the New Choices program stakeholders on programmatic improvements and how best to structure the program in the post-pandemic employment world., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A growing number of total knee arthroplasty (TKA) patients are candidates for same-day discharge (SDD). Previous research has shown that internet-based remote physical therapy (RPT) can produce equivalent outcomes to supervised outpatient physical therapy (OPT) after TKA. We sought to compare outcomes between RPT and OPT in patients undergoing SDD TKA using an electronic remote perioperative management (ERPM) program., Methods: Patients undergoing SDD TKA were enrolled in an ERPM program and randomized to ERPM + RPT or ERPM + OPT. Preoperative and 6-week functional assessments included knee range of motion, timed up and go, and 4-meter gait speed. Numerical Rating Scale pain scores were evaluated preoperatively, at 6 and 12 weeks, and satisfaction was assessed at 6, 12, and 52 weeks postoperatively. Participants completed the Veterans Rand 12 Item Health Survey and Knee Injury and Osteoarthritis Outcome Score preoperatively and at 6, 12, and 52 weeks postoperatively. OPT utilization was collected 90 days postoperatively., Results: Of 197 initially randomized patients, 76 remained in the ERPM + RPT group and 95 in the ERPM + OPT group after withdrawals and crossovers. Baseline characteristics showed no differences between the 2 groups. No clinically relevant differences were observed in knee range of motion, Numerical Rating Scale pain, patient-reported outcomes, functional assessments, or satisfaction at any follow-up time. Participants in the ERPM + OPT group attended an average of 11.57 physical therapy sessions, incurring a total cost of $462.8 and 133 minutes of travel. Conversely, the ERPM + RPT group experienced no expenses or travel time., Conclusions: Patients in the ERPM + RPT group had similar outcomes, lower costs, and saved time compared to patients in the ERPM + OPT group after SDD TKA. Further analysis is needed to determine predictive indicators for crossovers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4 + /CD8 + T cell response, poor cytokine production, insufficient neutralizing antibody (nAb) and poor response to HBsAg vaccination characterize CHB infection. The objective of this study was to develop virus-like-particles (VLPs) that elicit nAb to prevent viral spread and prime CD4 + /CD8 + T cells to eradicate intracellular HBV. Eight neutralizing B cell epitopes from the envelope PreS1 region were consolidated onto a species-variant of the HBV core protein, the woodchuck hepatitis core antigen (WHcAg). PreS1-specific B cell epitopes were chosen because of preferential expression on HBV virions. Because WHcAg and HBcAg are not crossreactive at the B cell level and only partially cross-reactive at the CD4 + /CD8 + T cell level, CD4 + T cells specific for WHcAg-unique T cell sites can provide cognate T-B cell help for anti-PreS1 Ab production that is not curtailed by immune tolerance. Immunization of immune tolerant HBV transgenic (Tg) mice with PreS1-WHc VLPs elicited levels of high titer anti-PreS1 nAbs equivalent to wildtype mice. Passive transfer of PreS1 nAbs into human-liver chimeric mice prevented acute infection and cleared serum HBV from mice previously infected with HBV in a model of CHB. At the T cell level, PreS1-WHc VLPs and hybrid WHcAg/HBcAg DNA immunogens elicited HBcAg-specific CD4 + Th and CD8 + CTL responses.

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.

Regulatory T (Treg) cells represent one of the main mechanisms of regulating self-reactive immune cells. Treg cells are thought to play a role in down-regulating immune responses to self or allogeneic antigens in the periphery. Although the function of Treg cells has been demonstrated in many experimental settings, the precise mechanisms and antigen specificity often remain unclear. In a hepatitis B e antigen-T-cell receptor (HBeAg-TCR) double transgenic mouse model, we observed a phenotypically unique (TCR+)  CD4- /CD8-  CD25(+/-)  GITR(high)  PD-1(high)  FoxP3-) HBeAg-specific population that demonstrates immune regulatory function. This HBeAg-specific double-negative regulatory cell population proliferates vigorously in vitro, in contrast to any other known regulatory population, in an interleukin-2-independent manner., (© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.)

Previous studies demonstrated that the primary APCs for the hepatitis B core Ag (HBcAg) were B cells and not dendritic cells (DC). We now report that splenic B1a and B1b cells more efficiently present soluble HBcAg to naive CD4(+) T cells than splenic B2 cells. This was demonstrated by direct HBcAg-biotin-binding studies and by HBcAg-specific T cell activation in vitro in cultures of naive HBcAg-specific T cells and resting B cell subpopulations. The inability of DC to function as APCs for exogenous HBcAg relates to lack of uptake of HBcAg, not to processing or presentation, because HBcAg/anti-HBc immune complexes can be efficiently presented by DC. Furthermore, HBcAg-specific CD4(+) and CD8(+) T cell priming with DNA encoding HBcAg does not require B cell APCs. TLR activation, another innate immune response, was also examined. Full-length (HBcAg(183)), truncated (HBcAg(149)), and the nonparticulate HBeAg were screened for TLR stimulation via NF-kappaB activation in HEK293 cells expressing human TLRs. None of the HBc/HBeAgs activated human TLRs. Therefore, the HBc/HBeAg proteins are not ligands for human TLRs. However, the ssRNA contained within HBcAg(183) does function as a TLR-7 ligand, as demonstrated at the T and B cell levels in TLR-7 knockout mice. Bacterial, yeast, and mammalian ssRNA encapsidated within HBcAg(183) all function as TLR-7 ligands. These studies indicate that innate immune mechanisms bridge to and enhance the adaptive immune response to HBcAg and have important implications for the use of hepadnavirus core proteins as vaccine carrier platforms.

Hepatitis B virus (HBV) expresses two structural forms of the nucleoprotein, the intracellular nucleocapsid (hepatitis core antigen [HBcAg]) and the secreted nonparticulate form (hepatitis e antigen [HBeAg]). The aim of this study was to evaluate the ability of HBcAg- and HBeAg-specific genetic immunogens to induce HBc/HBeAg-specific CD4(+)/CD8(+) T-cell immune responses and the potential to induce liver injury in HBV-transgenic (Tg) mice. Both the HBcAg- and HBeAg-specific plasmids primed comparable immune responses. Both CD4(+) and CD8(+) T cells were important for priming/effector functions of HBc/HBeAg-specific cytotoxic T-lymphocyte (CTL) responses. However, a unique two-step immunization protocol was necessary to elicit maximal CTL priming. Genetic vaccination did not prime CTLs in HBe- or HBc/HBeAg-dbl-Tg mice but elicited a weak CTL response in HBcAg-Tg mice. When HBc/HBeAg-specific CTLs were adoptively transferred into HBc-, HBe-, and HBc/HBeAg-dbl-Tg mice, the durations of the liver injury and inflammation were significantly greater in HBeAg-Tg recipient mice than in HBcAg-Tg mice. Importantly, liver injury in HBc/HBeAg-dbl-Tg mice was similar to the injury observed in HBeAg-Tg mice. Loss of HBeAg synthesis commonly occurs during chronic HBV infection; however, the mechanism of selection of HBeAg-negative variants is unknown. The finding that hepatocytes expressing wild-type HBV (containing both HBcAg and HBeAg) are more susceptible to CTL-mediated clearance than hepatocytes expressing only HBcAg suggest that the HBeAg-negative variant may have a selective advantage over wild-type HBV within the livers of patients with chronic infection during an immune response and may represent a CTL escape mutant.

Androgen receptor (AR) and glucocorticoid receptor (GR) influence distinct physiologic responses in steroid-responsive cells despite their shared ability to selectively bind in vitro to the same canonical DNA sequence (TGTTCT). While the DNA-binding domains (DBDs) of these receptors are highly conserved, the amino N-terminal domain (NTD) and hormone-binding domain (HBD) are evolutionarily divergent. To determine the relative contribution of these functional domains to steroid-specific effects in vivo, we constructed a panel of AR/GR gene fusions by interchanging the NTD, DBD, and HBD regions of each receptor and measured transcriptional regulatory activities in transfected kidney and prostate cell lines. We found that GR was approximately 10-fold more active than AR when tested with the mouse mammary tumor virus promoter, and that this difference in activity was primarily owing to sequence divergence in the NTDs. We also tested transcriptional activation of the androgen-dependent rat probasin promoter, and in this case, AR was at least twofold more active than GR. Analysis of the chimeric receptors revealed that this difference mapped to the DBD region of the two receptors. Transcriptional repression functions of the wild-type and chimeric receptors were measured using an activator protein 1 (AP-1) transrepression assay and identified the GR HBD as a more potent transrepressor of AP-1 transcriptional activation than the AR HBD. Taken together, our analyses reveal that evolutionary sequence divergence between AR and GR functional domains results in unique promoter-specific activities within biologic systems in which both AR and GR are normally expressed.

14C-diphacinone (0.2-1.5 mg/kg) was orally administered to rats and mice. Residue distribution in various tissues and radiocarbon elimination in feces and urine were determined. More than 60% of the administered radiocarbon was eliminated in feces and about 10% in urine in 4 days from mice and in 8 days from rats. The greatest amount of radioactivity in tissues of both rats and mice appeared in liver. Brain, muscle, blood, and fat had the lowest residue levels. Metabolites in feces and liver were chromatographically isolated and identified by mass spectrometry. In addition to unchanged diphacinone, four hydroxylated metabolites were identified in feces and liver. Hydroxylation occurred on either or both the indandione or phenyl rings. The positions of the hydroxy groups on the rings were not established.