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Development of the brain prenatally is affected by maternal experience and exposure. Prenatal maternal psychological stress changes brain development and results in increased risk for neuropsychiatric disorders. In this review, multiple levels of prenatal stress mechanisms (offspring brain, placenta, and maternal physiology) are discussed and their intersection with cellular stress mechanisms explicated. Heat shock factors and oxidative stress are closely related to each other and converge with the inflammation, hormones, and cellular development that have been more deeply explored as the basis of prenatal stress risk. Increasing evidence implicates cellular stress mechanisms in neuropsychiatric disorders associated with prenatal stress including affective disorders, schizophrenia, and child-onset psychiatric disorders. Heat shock factors and oxidative stress also have links with the mechanisms involved in other kinds of prenatal stress including external exposures such as environmental toxicants and internal disruptions such as preeclampsia. Integrative understanding of developmental neurobiology with these cellular and physiological mechanisms is necessary to reduce risks and promote healthy brain development., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Compounds targeting the sigma 2 receptor, which we recently cloned and showed to be identical with transmembrane protein 97 (σ2R/TMEM97), are broadly applicable therapeutic agents currently in clinical trials for imaging in breast cancer and for treatment of Alzheimer's disease and schizophrenia. These promising applications coupled with our previous observation that the σ2R/TMEM97 modulator SAS-0132 has neuroprotective attributes and improves cognition in wild-type mice suggests that modulating σ2R/TMEM97 may also have therapeutic benefits in other neurodegenerative conditions such as traumatic brain injury (TBI). Herein, we report that DKR-1677, a novel derivative of SAS-0132 with increased affinity and selectivity for σ2R/Tmem97 ( K i = 5.1 nM), is neuroprotective after blast-induced and controlled cortical impact (CCI) TBI in mice. Specifically, we discovered that treatment with DKR-1677 decreases axonal degeneration after blast-induced TBI and enhances survival of cortical neurons and oligodendrocytes after CCI injury. Furthermore, treatment with DKR-1677 preserves cognition in the Morris water maze after blast TBI. Our results support an increasingly broad role for σ2R/Tmem97 modulation in neuroprotection and suggest a new approach for treating patients suffering from TBI.

Increasing atmospheric CO₂ concentrations alter leaf physiology, with effects that cascade to communities and ecosystems. Yet, responses over cycles of disturbance and recovery are not well known, because most experiments span limited ecological time. We examined the effects of CO₂ on root growth, herbivory and arthropod biodiversity in a woodland from 1996 to 2006, and the legacy of CO₂ enrichment on these processes during the year after the CO₂ treatment ceased. We used minirhizotrons to study root growth, leaf censuses to study herbivory and pitfall traps to determine the effects of elevated CO₂ on arthropod biodiversity. Elevated CO₂ increased fine root biomass, but decreased foliar nitrogen and herbivory on all plant species. Insect biodiversity was unchanged in elevated CO₂. Legacy effects of elevated CO₂ disappeared quickly as fine root growth, foliar nitrogen and herbivory levels recovered in the next growing season following the cessation of elevated CO₂. Although the effects of elevated CO₂ cascade through plants to herbivores, they do not reach other trophic levels, and biodiversity remains unchanged. The legacy of 10 yr of elevated CO₂ on plant-herbivore interactions in this system appear to be minimal, indicating that the effects of elevated CO₂ may not accumulate over cycles of disturbance and recovery., (© 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.)

Uncertainty surrounds belowground plant responses to rising atmospheric CO₂ because roots are difficult to measure, requiring frequent monitoring as a result of fine root dynamics and long-term monitoring as a result of sensitivity to resource availability. We report belowground plant responses of a scrub-oak ecosystem in Florida exposed to 11 yr of elevated atmospheric CO₂ using open-top chambers. We measured fine root production, turnover and biomass using minirhizotrons, coarse root biomass using ground-penetrating radar and total root biomass using soil cores. Total root biomass was greater in elevated than in ambient plots, and the absolute difference was larger than the difference aboveground. Fine root biomass fluctuated by more than a factor of two, with no unidirectional temporal trend, whereas leaf biomass accumulated monotonically. Strong increases in fine root biomass with elevated CO₂ occurred after fire and hurricane disturbance. Leaf biomass also exhibited stronger responses following hurricanes. Responses after fire and hurricanes suggest that disturbance promotes the growth responses of plants to elevated CO₂. Increased resource availability associated with disturbance (nutrients, water, space) may facilitate greater responses of roots to elevated CO₂. The disappearance of responses in fine roots suggests limits on the capacity of root systems to respond to CO₂ enrichment., (© 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.)

Sharks and other large predators are scarce on most coral reefs, but studies of their historical ecology provide qualitative evidence that predators were once numerous in these ecosystems. Quantifying density of sharks in the absence of humans (baseline) is, however, hindered by a paucity of pertinent time-series data. Recently researchers have used underwater visual surveys, primarily of limited spatial extent or nonstandard design, to infer negative associations between reef shark abundance and human populations. We analyzed data from 1607 towed-diver surveys (>1 ha transects surveyed by observers towed behind a boat) conducted at 46 reefs in the central-western Pacific Ocean, reefs that included some of the world's most pristine coral reefs. Estimates of shark density from towed-diver surveys were substantially lower (<10%) than published estimates from surveys along small transects (<0.02 ha), which is not consistent with inverted biomass pyramids (predator biomass greater than prey biomass) reported by other researchers for pristine reefs. We examined the relation between the density of reef sharks observed in towed-diver surveys and human population in models that accounted for the influence of oceanic primary productivity, sea surface temperature, reef area, and reef physical complexity. We used these models to estimate the density of sharks in the absence of humans. Densities of gray reef sharks (Carcharhinus amblyrhynchos), whitetip reef sharks (Triaenodon obesus), and the group "all reef sharks" increased substantially as human population decreased and as primary productivity and minimum sea surface temperature (or reef area, which was highly correlated with temperature) increased. Simulated baseline densities of reef sharks under the absence of humans were 1.1-2.4/ha for the main Hawaiian Islands, 1.2-2.4/ha for inhabited islands of American Samoa, and 0.9-2.1/ha for inhabited islands in the Mariana Archipelago, which suggests that density of reef sharks has declined to 3-10% of baseline levels in these areas., (©2012 Society for Conservation Biology No claim to original US government works.)

This study consisted of a 28-day oral repeat dose (repeat dose toxicity [RDT]) phase and a developmental and reproductive (developmental and reproductive toxicity [DART]) phase with rats. Rats were treated with Dechlorane Plus at doses of 0, 750, 1500, or 5000 mg/kg by gavage. For the RDT phase, no effects were observed on in-life parameters or clinical or anatomic pathology. In the DART phase, no effects were observed on reproductive or fertility indices, or fetal development through lactation day (LD) 4. No effects were noted on gestation day (GD) 20 implantation data, fetal indices, or external and visceral examinations. Mortalities occurred across all dose groups, although these were gavage-related errors and not compound related. Microscopic evidence of gavage-related errors included adhesions, inflammation, and fibrosis in the thoracic and pleural cavities. These findings were not test article related as they were observed only in animals with evidence of gavage injury. The no-observable-effect level (NOEL) in both phases of study was 5000 mg/kg., (© The Author(s) 2010)

Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to a number of agents than other rat strains and the results of this study suggest that this may contribute, along with pharmacokinetic differences, to the inflammatory response of F-344 rats to dietary MHCs., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Urogenital abnormalities are among the most common of all human birth defects. In developmental toxicity studies with the Syk kinase inhibitor R788, a spectrum of findings, including renal agenesis, were observed. R788 has also been found to inhibit the receptor tyrosine kinase Ret. Ret kinase is known to be an essential component in the signaling pathway required for renal organogenesis and ureteric duct formation. Previously known is that mutant mice without the c-ret gene, develop urogenital malformations including renal agenesis., Methods: In GLP developmental toxicity studies, gravid rabbits were treated orally with R788 at doses of 0, 10, 22, and 50 mg/kg/day (gestation days 7-19) and gravid rats received 0, 5, 12.5, and 25 mg/kg/day (gestation days 6-17) by the same route. The activity of R406 against Ret kinase was assessed in biochemical and cell-based assays., Results: A dose-dependent increase in malformations, including renal and ureteric agenesis and a specific major vessel anomaly, retroesophageal right subclavian artery, was observed in both the rat and rabbit. R788 proved to be a potent inhibitor of Ret kinase., Conclusions: R788 promoted a spectrum of developmental toxicity, including renal and ureteric agenesis and a specific major vessel abnormality, retroesophageal right subclavian artery, in two different species. These effects are likely the result of inhibition of Ret kinase given its importance in the normal ontogeny of the urogenital and cardiovascular systems across species., ((c) 2008 Wiley-Liss, Inc.)

Effective conservation requires rigorous baselines of pristine conditions to assess the impacts of human activities and to evaluate the efficacy of management. Most coral reefs are moderately to severely degraded by local human activities such as fishing and pollution as well as global change, hence it is difficult to separate local from global effects. To this end, we surveyed coral reefs on uninhabited atolls in the northern Line Islands to provide a baseline of reef community structure, and on increasingly populated atolls to document changes associated with human activities. We found that top predators and reef-building organisms dominated unpopulated Kingman and Palmyra, while small planktivorous fishes and fleshy algae dominated the populated atolls of Tabuaeran and Kiritimati. Sharks and other top predators overwhelmed the fish assemblages on Kingman and Palmyra so that the biomass pyramid was inverted (top-heavy). In contrast, the biomass pyramid at Tabuaeran and Kiritimati exhibited the typical bottom-heavy pattern. Reefs without people exhibited less coral disease and greater coral recruitment relative to more inhabited reefs. Thus, protection from overfishing and pollution appears to increase the resilience of reef ecosystems to the effects of global warming.

Time-mated Sprague-Dawley rats were exposed whole body to analytically measured 3-(methylthio) propionaldehyde (3-MTP) vapor concentrations of 0 (air controls), 9.87, 58.3 and 127.8 ppm over gestational days (gd) 6-15 for 6 h day(-1). There was an exposure concentration-related maternal toxicity (clinical signs, body weight change and food consumption) that was marginal at 9.87 ppm. No effects on gestational parameters, fetal numbers and sex ratio or fetal body weights were noted. There was no increase in the incidence of either malformations or variations (total, external, visceral or skeletal). Thus, the no-observed-adverse-effect level (NOAEL) for development toxicity for exposure to 3-MTP vapor was 127.8 ppm., (Copyright 2005 John Wiley & Sons, Ltd)

Vinyl chloride (VC) exposure is primarily via inhalation in the workplace. The primary target organ of VC toxicity is the liver and occupational exposure to VC leads to hepatic angiosarcoma. However, based on epidemiological studies, researchers have been unable to ascertain the effect of occupational VC exposure on embryo-fetal development or reproductive function. A limited number of animal studies available in the literature have examined the effect of VC on embryo-fetal development, however, there are no published studies on the effect of VC exposure on reproductive capability. The current study was designed to assess the potential maternal and/or embryo-fetal developmental and 2-generation reproductive toxicity of inhaled VC in CD(R) Sprague-Dawley rats at exposure levels of 0, 10, 100, and 1100 ppm. In the embryo-fetal/developmental toxicity study, the female rats were exposed to VC daily from gestation day (GD) 6 through 19. In the reproductive toxicity study, the F(0) generation male and female rats were exposed to VC for a 10-week premating and 3-week mating periods. The F(0) generation male rats were exposed to VC until terminal euthanasia. The F(0) generation female rats were exposed from GD 0 through GD 20 and lactation day (LD) 4 through LD 25. Our results indicate that up to 1100 ppm VC exposure did not adversely affect embryo-fetal developmental or reproductive capability over 2 generations in rats. The primary target organ of VC, the liver, was affected as evidenced by an increase in liver weight and/or histologically identified cellular alterations, such as centrilobular hypertrophy at 100 and 1000 ppm. Based on the results of these studies, the no observed adverse effect level (NOAEL) for embryo-fetal/development is 1100 ppm, and the NOAEL for reproduction is 1100 ppm. The results from the current studies, which are a more comprehensive embryo-fetal/developmental and reproduction study, may be incorporated into future risk assessments of occupational exposure to VC where concerns regarding the effects of VC exposure remain.

Most healthcare organizations can ill afford to assume risk for which they are inadequately compensated. When capital projects are being considered, factoring risk with an adjustment to the projected cost of capital can increase the calculated return on investment and improve the net present value of anticipated cash flow. This adjustment factor, however, should reflect the capital structure of the organization, historical average returns, and variance in the context of the market, the specific industry, and similar projects being considered.

A distillate of light catalytic cracked naphtha (CAS number 64741-55-5, LCCN-D), administered by inhalation, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, following a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. LCCN-D was administered as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to female rats for approximately 7 wk from 2 wk prior to mating, during mating through gestational d 19, and to males beginning 2 wk prior to mating for 8 consecutive weeks. Dams and litters were sacrificed on postnatal d 4, and males were sacrificed within the following week. Parental systemic effects observed at the 7500 ppm exposure level were increased kidney weights and relative liver weights in males and increased spleen weights in high-dose females. Livers and spleens from rats in the high-dose group were normal in appearance at necropsy. IncreaSed kidney weights in high-dose males were indicative of male-rat-specific light hydrocarbon nephropathy. No test-related microscopic changes were observed in the reproductive organs or nasal turbinate tissues of either sex. Reproductive performance was unaffected by treatment with LCCN-D. Fertility index was > or =90% in all dose groups. There were no exposure-related differences in implantation sites and live pups per litter, and no gross abnormalities were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or =97%; the high-dose group had more male than female pups at birth and at d 4 postpartum. Under the conditions of this study, the no-observable-adverse-effect level (NOAEL) for exposure to light catalytic cracked naphtha distillate for parental toxicity was 2500 ppm and the NOAEL for reproductive performance and developmental toxicity was 7500 ppm.

Communication can be thought of as a message that is sent, received, and understood. Each discipline of the health profession has its own jargon and means of expressing ideas in shorthand. These separate forms of communicating are effective among those of the same background but are often at the root of misunderstandings between professional groups. This article reviews communication theory and traces the difficulties created when inter-disciplinary teams of healthcare try to work together and communicate. As multi-disciplinary teams are increasingly dealing with the complex problems of today's healthcare system, clear communication and understanding has never been more important. If educators could assist in creating an understanding of vocabulary used for decision processes, communication could improve. The authors of this study performed a multi-stage Delphi survey that grouped terms used by administrators and clinicians and produced a lexicon of corresponding terms. An expert panel then reviewed and modified the list. The result is a lexicon that can be useful to assist clinicians and administrators to communicate with each other. By utilizing clinical terminology, or vice versa, instead of management or clinical jargon, some of the translation done by administration or clinicians could be reduced. Examples of how the lexicon can be utilized are provided in the article. This includes using it in health administration education to demonstrate the variances in clinical/managerial terms. It could also be provided as a primer to physicians, nurses, and other health professionals who assume administrative positions to enhance their communication with administrators.

D-tagatose is a low-calorie sweetener that tastes like sucrose. The developmental toxicity of D-tagatose was investigated in Crl:CD(SD)BR rats administered D-tagatose at three dose levels (4000, 12,000, and 20,000 mg/kg body wt/day) via gastric intubation on days 6-15 of gestation. No compound-related toxicity was seen among any of the maternal groups. No treatment-related clinical effects were seen in the maternal animals at the 4000 mg/kg/day dose level. At the mid- and high-dose levels, most maternal animals had unformed or watery stools; this effect was most prominent early in the treatment period (Gestation Days 6-8). This effect was attributed to the osmotic effect of the large amount of D-tagatose given to the animals at these doses. Since D-tagatose is not digested or absorbed to a large extent, most of the sugar passes into the colon where it absorbs water and is fermented by colonic bacteria. Mean weight gain for the low- and mid-dose animals was comparable to the control; however, the high-dose group experienced a mean weight loss over the Gestation Day 6-9 interval. Over the entire treatment interval, however, mean weight gain for the high-dose animals was comparable to control. The decreased weight gain in the high-dose animals during the Gestation Day 6-9 interval was considered to be a direct result of laxation. In addition to the effect of laxation on body weight, reduced food consumption also contributed to the decreased weight gain. In the low-dose animals, no effect on food consumption was seen; however, both mid- and high-dose animals had food consumption values that were statistically significantly lower than the control. Food consumption was lowest during the Gestation Day 6-9 interval, the period when laxation was most prominent. Food consumption rebounded and was statistically significantly higher than the control for the mid- and high-dose animals during the posttreatment interval. Maternal liver weight for the low-dose animals was comparable to the control. However, a statistically significant increase in mean maternal liver weight was noted for the mid-and high-dose animals. Based on a lack of any corresponding histopathology, the increased liver weights were not considered toxicologically significant. There were no adverse effects on reproductive performance noted in any treatment group. No adverse treatment-related fetal effects on fetal weight, sex distribution, liver weight, or external, skeletal, or visceral malformations were noted at any dose level., (Copyright 1999 Academic Press.)

Health care organizations have traditionally selected capital projects based on subjective measures such as medical staff priority, accreditation criteria, and regulations. In some cases, basic qualitative measures, such as payback period or profitability indices, have been used. The expected reduction in available capital that will result from changes in Medicare reimbursement and from managed care, as well as increased competition, will require health care decision makers to adopt more sophisticated methods of capital project evaluation in the future if they expect their organizations to remain viable. This article demonstrates, through the use of microcomputers and commonly used spreadsheet software, that the capital selection decision process can be improved and the optimal combination of projects, from a financial perspective, selected.

To determine the cellular adaptations to fetal hyperglycemia and hypoglycemia, we examined the time-dependent effects on basal (GLUT-1 and GLUT-3) and insulin-responsive (GLUT-4) glucose transporter proteins by quantitative Western blot analysis in fetal ovine insulin-insensitive (brain and liver) and insulin-sensitive (myocardium, skeletal muscle, and adipose) tissues. Maternal glucose infusions causing fetal hyperglycemia resulted in a transient 30% increase in brain GLUT-1 but not GLUT-3 levels and a decline in liver and adipose GLUT-1 and myocardial and skeletal muscle GLUT-1 and GLUT-4 levels compared with gestational age-matched controls. Maternal insulin infusions leading to fetal hypoglycemia caused a decline in brain GLUT-3, an increase in brain GLUT-1, and a subsequent decline in liver GLUT-1, with no significant change in insulin-sensitive myocardium, skeletal muscle, and adipose tissue GLUT-1 or GLUT-4 concentrations, compared with gestational age-matched sham controls. We conclude that fetal glucose transporters are subject to a time-dependent and tissue- and isoform-specific differential regulation in response to altered circulating glucose and/or insulin concentrations. These cellular adaptations in GLUT-1 (and GLUT-3) are geared toward protecting the conceptus from perturbations in substrate availability, and the adaptations in GLUT-4 are geared toward development of fetal insulin resistance.

A recent MGMA survey showed work-life balance as the number one issue facing group practice managers. This article explains techniques from the field of time management that will enable group practice managers to gain control of their schedules, reduce time pressures and stress and increase productivity. The article covers: goal setting, daily lists, handling paperwork, delegating and limiting involvement, socializing, communicating, overachieving, planning, writing, telephone calling, attending meetings, reading, financial planning, developing a philosophy, involving family, evaluating skills and teaching time management to employees.

Glucose, an essential substrate for brain oxidative metabolism, is transported across the blood-brain barrier and into neuronal and glial cells via Glut 1 and Glut 3 facilitative glucose transporter isoforms. To examine the effect of excessive circulating glucose on fetal brain glucose transporter expression, we investigated the effect of streptozotocin-induced maternal diabetes (SEVERE-D; n = 29) on the 20-d gestation fetal rat brain Glut 1 and Glut 3. We studied the effect of streptozotocin alone (STZ-ND; n = 12) in a nondiabetic state as well, along with vehicle injected controls (C; n = 24). In the presence of fetal hyperglycemia (12.63 +/- 0.82 nM-SEVERE-D versus 2.35 +/- 0.28-STZ-ND and 2.42 +/- 0.16-C; p < 0.001) and hypoinsulinemia (0.38 +/- 0.03 nM-SEVERE-D versus 0.50 +/- 0.07-STZ-ND and 0.55 +/- 0.06-C; p < 0.02), no detectable change in fetal brain Glut 1 and Glut 3 pretranslational expression (transcription/elongation rates and corresponding steady state mRNA levels) was noted when simultaneously compared with the STZ-ND and C groups. In contrast, a trend toward a decline in Glut 1 (approximately 25 to 30%, p = 0.05) and a substantive decrease in Glut 3 (approximately 35 to 50%, p = 0.0006) protein concentrations was present in both the STZ-ND and SEVERE-D groups when compared with the C group. These observations support a chemical effect of streptozotocin independent of maternal diabetes upon the translation or posttranslational processing of fetal brain glucose transporters. Maternal diabetes with fetal hyperglycemia, however, failed to substantively alter fetal brain glucose transporters independent of the streptozotocin effects upon neuroectodermally derived tissues. We conclude that maternal diabetes with associated overt fetal hyperglycemia does not significantly change fetal brain glucose transporter levels.

We investigated the effect of streptozotocin-induced short-term maternal diabetes upon fetal rat myocardial and skeletal muscle glucose transporter Glut 1 (basal form) and Glut 4 (insulin-responsive form) protein concentrations by Western blot analysis. In the severely diabetic group (SEVERE-D, n = 17), a 3-fold increase in maternal and fetal glucose concentrations (p < 0.01) was associated with a 3-fold decline in maternal (p < 0.01) with no change in fetal insulin levels when compared with the streptozotocin-treated nondiabetic (n = 10) and vehicle-treated control (control, n = 14) groups. These changes in the SEVERE-D group when compared with controls were associated with a 30 and 65% decline, respectively, in fetal myocardial and skeletal muscle (forelimb and hind limb) Glut 1 protein concentrations. The fetal myocardium also demonstrated a 45% decline in Glut 4 protein levels. Fetal skeletal muscle Glut 4 protein, which was expressed only at very low levels in controls showed no change in SEVERE-D. Immunohistochemical analysis revealed a myocyte-plasma membrane association of Glut 1 and an intracellular Glut 4 distribution in the fetal myocardium and skeletal muscle. No Glut 1 immunoreactivity was noted in either the fetal myocardial or skeletal muscle perineural sheaths, blood vessels, or the entrapped fetal red blood cells. This subcellular localization pattern was unaltered in all three treatment groups. We conclude that maternal diabetes causing fetal hyperglycemia with normoinsulinemia suppresses fetal myocardial Glut 1 and Glut 4 and fetal skeletal muscle Glut 1. The decline in the plasma membrane associated Glut 1 concentrations may serve a protective function by reducing the glucose transport rate into fetal myocardial and skeletal muscle cells, which otherwise could be vulnerable to high circulating glucose. The in-utero maternal diabetes induced decrease in fetal myocardial intracellular-Glut 4 concentration could herald the emergence of insulin resistance.

HCFC 123 is one of the chemicals being developed as a replacement for CFC 11 in refrigerant and solvent applications. Supplementing earlier rat teratology studies, a rabbit inhalation teratology study was conducted. In addition, one-generation and two-generation inhalation reproduction studies were conducted. In the teratology study, the pregnant rabbits were exposed to levels of 0 (control), 500, 1500, and 5000 ppm, 6 hr per day from Days 6 through 18 of gestation. Slight body weight losses and reduced food consumption were seen in does in all three exposure level groups. This response followed an exposure-related pattern. There were no other signs of maternal toxicity. There was also no evidence of treatment-related effects on the kits. A probe one-generation reproduction study was conducted. In this study four groups of 12 male and 12 female rats were exposed to vapors of HCFC 123 6 hr per day, 7 days per week from 4 weeks prior to mating through weaning of their offspring. The exposure levels for this study were 0 (control), 300, 1000, and 5000 ppm. There were no effects on mating and fertility, or on pup survival or birth weight. A two-generation study was subsequently conducted. In this study, five groups of 32 male and female rats were exposed to HCFC 123 from 6 weeks of age through weaning. From the offspring of these animals, groups of 28 males and females were selected for the F1 generation. These animals were exposed to HCFC 123 from weaning (4 weeks of age) through weaning of the F1 generation. All exposures were 6 hr per day, 7 days per week. The exposure levels for this study were 0 (control), 30, 100, 300, and 1000 ppm. There were no effects on any of the fertility or reproductive indices measured. As with prior studies, decreases in serum triglyceride levels were seen. Pup survival and birth weight were unaffected by treatment. Pup body weight gain was lower in all treatment groups during nursing, following an exposure-related pattern. Since weight gain for the F1 animals was normal following weaning, this depression of body weight gain may be related to the depression of serum triglycerides. In addition, liver weights of the adult rats exposed to levels of 100 ppm and higher of HCFC 123 were higher than controls, histological examination revealed only hepatic enlargement and vacuolation. It was concluded that exposure to HCFC 123 did not cause reproductive effects although it did effect the body weight gain of the offspring during lactation.

Inhalation studies were conducted to determine the potential toxicity of HCFC-124. Groups of rats and mice were exposed to HCFC-124 6 hr/day, 5 days/week for 13 weeks at 0, 5000, 15,000, and 50,000 ppm. Subgroups of rats and mice were held for a 1-month recovery period. A functional observational battery (FOB) was conducted on rats at 0, 4, 13, and 16 weeks. Clinical pathology evaluations were conducted at 7, 13, and 17 weeks. Thirteen or 17 weeks after study initiation, rats and mice underwent gross and microscopic evaluation, and livers were evaluated for hepatic beta-oxidation activity. In addition, groups of female rats and rabbits were exposed to HCFC-124 by inhalation during gestation to 0, 5000, 15,000, or 50,000 ppm. Exposure of rats and mice to HCFC-124 caused minimal compound-related effects. Compound-related changes occurred in several clinical pathology parameters in rats and mice. Hepatic beta-oxidation activity was significantly higher in 5000, 15,000, and 50,000 ppm male mice; however, there were no compound-related effects on beta-oxidation activity in rats. During the daily exposures, rats, mice, and rabbits exposed to 50,000 ppm were less responsive to auditory stimuli or less active compared to controls. At the 13-week FOB, male rats exposed to 15,000 or 50,000 ppm had decreased arousal. There were no compound-related effects on mortality, clinical signs, ocular tissues, hematology parameters, organ weights, and tissue morphology at any concentration in rats or mice. Maternal toxicity in rats was evident by a significant decrease in weight gain and food consumption at 50,000 ppm. Similarly, 50,000 ppm pregnant rabbits had lower food consumption. However, for both rats and rabbits, there was no evidence of fetal toxicity at any concentration.

Rapid evolution of the health care industry forces managers to make cost-effective decisions. Typical hospital cost accounting systems do not provide emergency department managers with the information needed, but emergency department settings are so complex and dynamic as to make the more accurate activity-based costing (ABC) system prohibitively expensive. Through judicious use of the available traditional cost accounting information and simple computer spreadsheets. managers may approximate the decision-guiding information that would result from the much more costly and time-consuming implementation of ABC.

The purposes of this article are to identify all the variables that impact productivity in a group practice, contrast the administrator's and physician's definitions of productivity, discuss current measurement tools and outline the steps in a traditional productivity project. The article identifies key variables that management must address: physician education, goals, feedback and rewards that are critical to the success of any productivity undertaking. Upon completion of this article, the reader will be able to understand the differences in the way administrators and physicians view productivity and be able to identify the vital areas that must be addressed in any effort to increase productivity. While the article focuses on the academic setting, the principles are applicable in any group practice.

Objective: Maternal diabetes alters placental glucose metabolism and maternofetal glucose transport. The purpose of this study was to determine whether genes involved in placental glucose uptake and transport were concomitantly altered, resulting in the observed changes in the state of maternal diabetes., Study Design: By means of the nonobese diabetic pregnant mouse we examined the expression of placental glucose transporters, hexokinase I, glycogen content, glycogen-regulating enzyme activities in control animals (blood glucose 8.5 +/- 0.2 mmol/L, n = 25), moderate maternal diabetes (blood glucose 10 to 13.9 mmol/L, n = 16), and severe maternal diabetes (blood glucose > 16.7 mmol/L, n = 12). Comparisons by the analysis of variance and the Newman-Keuls test were performed., Results: Although changes in placental glucose transporters and hexokinase I messenger ribonucleic acid levels occurred, neither state of diabetes altered the corresponding protein levels. Changes in placental deoxyribonucleic acid (p < 0.05) and glycogen content (p < 0.01), fetal insulin levels (p < 0.02), and fetal size (p < 0.05) occurred in the moderately diabetic group, and changes in placental weight (p < 0.05) and fetal glucose levels (p < 0.02) were observed in the severely diabetic group., Conclusions: Placental glucose transporting and phosphorylating protein levels by themselves do not regulate diabetes-induced fetoplacental alterations. The lack of a protective decline in these proteins may account for the observed fetoplacental adaptations to excess glucose.

The effects of hydroquinone (HQ) on reproductive performance and fertility were assessed in a two-generation study with CD Sprague-Dawley rats (one litter per generation). HQ was administered in an aqueous solution by gavage at doses of 0, 15, 50, and 150 mg/kg/day. F0 and F1 parental animals were dosed daily for at least 10 weeks prior to cohabitation, during cohabitation, and until scheduled termination. At all dose levels tested, no adverse effects were observed on feed consumption, survival, or reproductive parameters for the F0 or F1 parental animals. Mild, transient tremors were observed shortly after dosing at 150 mg/kg/day in several F0 and F1 parental animals and in a single F0 male at 50 mg/kg/day. These tremors occurred infrequently and were considered to be due to an acute stimulatory effect of HQ on the nervous system. Body weights for F0 and F1 parental females were similar between all dose groups throughout the study. Body weights for F0 parental males were also comparable to those of control throughout the study. Statistically significant differences in body weights were noted for the F1 parental males in the 50 and 150 mg/kg/day dose groups at several intervals during the premating, mating, and postmating periods. No treatment-related effects on pup weight, sex distribution, or survival were noted for pups of either generation. Upon postmortem examination, no treatment-related gross lesions were observed in either the F0 or F1 parental animals or their weanlings. Histopathologic examination of reproductive tissues and pituitary glands from high-dose F0 and F1 parental animals did not reveal any changes related to treatment with HQ.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes alters adult brain glucose uptake and glucose transporter 1 gene expression. To investigate the effect of diabetes on genes regulating fetal brain glucose uptake, we examined the effect of moderate (blood glucose 10-16.7 mM, normoinsulinemia) and severe (blood glucose > 16.8 mM, hypoinsulinemia) maternal diabetes on the expression of genes regulating fetal brain glucose uptake in the genetically nonobese diabetic mouse. In the moderately diabetic state, a 50% decline in fetal brain GLUT1 mRNA levels was associated with a 20% increase in the corresponding GLUT1 protein levels. Simultaneously, although fetal brain GLUT3 mRNA and protein levels were barely detectable, no change in hexokinase I enzyme mRNA, protein (115,000 and 100,000 M(r)) or activity, was noted. In the severe form of maternal diabetes GLUT1 protein was unchanged, GLUT3 protein levels remained low, and a 2- to 3-fold increase in the lower molecular form of the hexokinase I protein (100,000 M(r)) and enzyme activity occurred. These observations suggest that moderate and severe forms of maternal diabetes do not affect the fetal brain glucose transporter levels to a physiologically significant extent. The severe form of maternal diabetes, however, enhances 1.5- to 3-fold the expression and activity of hexokinase I. This enzyme mediates the rate-limiting step in brain glucose metabolism, namely the intracellular conversion of glucose to glucose-6-phosphate.

This article analyzes the implementation of a traditional Economic Grand Rounds (EGR) program in a teaching hospital. The conclusions are that the original concepts of EGR--presentations of treatment costs by clinicians in a grand rounds setting, reinforcement of agreed changes in practice patterns, and subsequent evaluation and participation--are still valid but are inadequate to ensure a successful program. Other factors must be added if EGR is to attain its goals. These factors are administrative and nursing involvement, a provision to make policy changes, and incentives for the medical staff. This article also outlines areas of potential savings achieved through an EGR program in laboratory testing, preoperative laboratory testing, and intravenous therapy with antibiotics.

To obtain information on potential developmental toxicity, hydroquinone (HQ) was administered to pregnant New Zealand White rabbits (18 mated per dose group) in aqueous solution (0, 25, 75, or 150 mg HQ/kg/day) by gavage on Gestation Days (GD) 6 to 18. Caesarean sections were performed on GD 30. Doses of 75 and 150 mg/kg/day adversely affected feed consumption and/or body weights of dams during the treatment period. At these doses, however, treatment-related effects were not evident from physical observations, liver and kidney weights, premature delivery incidence, and caesarean sectioning data. The NOEL for maternal toxicity was 25 mg/kg/day. In the 150 mg/kg/day dose group, total incidences of external, visceral, and skeletal findings for fetuses did not differ statistically from controls. Slight, statistically insignificant, increases were found, however, in the incidences of ocular and minor skeletal malformations (micro-ophthalmia, vertebral/rib defects, angulated hyoid arch) on both a per fetus and a per litter basis. Under the conditions of this study, HQ at 150 mg/kg/day produced minimal developmental alterations in the presence of maternal toxicity. The NOEL for developmental toxicity was 75 mg/kg/day.

Alkylate 215, a mixture of linear decyl- to tridecylbenzenes, is an intermediate in the manufacture of detergent sulfonates. A two-generation reproduction study and a developmental toxicity study were conducted using single daily doses given by gastric intubation in a corn oil vehicle. In the reproduction study, groups of 30 rats/sex/group were given doses of 0, 5, 50, or 500 mg/kg/day. F0 animals received a 10-week premating treatment period and were then mated to produce a single litter; F1 adults were selected from the F1 litters. F1 animals were dosed for 11 weeks before mating to produce a single litter. Adults and weaned pups received a gross postmortem examination. Histopathology studies were conducted on reproductive tissues, tissues with gross lesions, and the pituitary gland taken from each adult in the control and high dose groups. In the developmental toxicity study, groups of 24 mated female rats were given 0, 125, 500, or 2000 mg/kg/day on Days 6 through 15 of gestation. Dams were terminated on gestation Day 20 and fetuses were examined for external, soft tissue, and skeletal defects. Results of the reproduction study were as follows. At 50 mg/kg/day, pup weights were decreased at Day 7 in the F1 litter. At 500 mg/kg/day, decreases were found in the F0 females in premating and early lactation weight gains; in both generations in premating weight gains in males and in weight gains during gestation in females; and in litter size, pup viability at birth, Day 0-4 survival, and pup weights on Days 14 and 21. The NOAEL for reproductive effects was 5 mg/kg/day. The developmental toxicity study found effects on several parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimethylformamide (DMF) is a widely used industrial solvent. DMF has been reported to be a developmental toxin when given to rodents by injection or following dermal administration. In this study, groups of pregnant rats were exposed by inhalation to either 0 (control), 30, or 300 ppm DMF from gestation day 6 through 15. In the 300 ppm rats, both maternal weight gain during gestation and fetal weights were lower than those of the controls. Fetal resorptions were not increased in this group. No significant differences among either maternal or fetal rats were seen in the 30 ppm group compared to controls. Both fetal and maternal toxicity were noted at 300 ppm and the no observed effect level under these experimental conditions was 30 ppm for both the dams and the conceptuses. DMF did not produce malformations in the rat fetus even at a level that was toxic to the dam.

Groups of 15 male and 15 female Sprague-Dawley rats were exposed to 1 of 3 chloropropene (2,3-Di = DCP; 1,2,3-Tri = TRCP; and 1,1,2,3-Tetra = TECP) vapors to provide information on repeated exposures and the potential for reproductive impairment by the most likely route of occupational exposure. Target exposure concentrations were 0, 1, 5, and 15 ppm, 6 h/d, 5 d/wk for 13 wk. The following parameters were evaluated: pharmacotoxic signs, survival, body weights, hematology, clinical blood chemistry, urine analysis, gross and histopathology (over 40 tissues/rat), organ weights, and selected weight ratios. Signs of nasal irritation were noted in rats exposed to 15 ppm of either DCP or TRCP but not TECP. Small decreases in overall body weight were observed in female rats exposed to 15 ppm TCP. An increase (approximately 15%) in spleen weight, with no corresponding histopathological or clinical findings, was observed in 15 ppm DCP-treated male rats. No other effects considered related to treatment were observed following exposure to any of the three chlorinated propenes. Additional groups of 10 male and 20 female Sprague-Dawley rats were exposed to DCP, TRCP, or TECP vapors at target concentrations of 0, 1, or 5 ppm for 6 h/d, 5 d/wk for a 10-wk premating period, a mating period, and the first 14 d (females only) of gestation. Females were allowed to deliver litters and the offspring were evaluated during a 21-d lactation period. Mating, pregnancy, and fertility indices were generally comparable among all test groups, although female mating and pregnancy indices of both DCP-treated females were lower than expected in the regular and postrecovery reproduction phase. No effects were seen on pup survival, sex distribution, body weights, organ weights, and ratios. A modest reduction in pup body weights was observed following TECP exposure but was attributed to large litter size. No treatment-related effects were seen following necropsy of adults or weanlings, nor were such effects noted following microscopic evaluation of gonads from parental animals.

Dose levels for these studies were selected mainly on the basis of subchronic studies, although consideration was also given to workplace exposure levels and proposed mechanism of tumor formation with structurally similar compounds. For the chronic study, groups of 60 male and 60 female Sprague-Dawley CD (Registered Trademark of Charles River Breeding Laboratories, Portage, MI) rats were given 0, 0.25, 1.5, or 9.0 mg/kg/day paranitroaniline (PNA) by gavage in corn oil for a period of 2 years. Parameters monitored included clinical observations, ophthalmoscopic exams, body weights, food consumption, hematology, clinical chemistry, and urinalysis at regular intervals throughout the study. All gross lesions and over 40 tissues were examined histologically for all control and high-dosage-level animals. Gross lesions, spleens, and livers of low- and mid-dosage groups were also examined histologically. For the reproduction study, groups of 15 male and 30 female rats, designated as F0 generation, were given PNA at the same levels as the chronic study for 14 weeks prior to mating and during mating, gestation, and lactation. Selected groups of 15 male and 30 female rats of the F1 generation received the same dose of PNA for 18 weeks prior to mating and during mating, gestation, and lactation. F2 pups were observed through weaning at which time they were euthanized. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. In the chronic study, except for a slight decrease in survival of high-dose male rats late in the study, survival in all treated groups was comparable to controls. Blood methemoglobin levels were elevated in the mid- and high-dosage groups, while slight anemia was observed in the high-dosage group also. Spleen weights were significantly increased in the high-dosage groups. An accumulation of brown pigment was observed in the cytoplasm of the sinusoidal macrophages or littoral cells of the liver and in the reticuloendothelial cells of the spleen. No treatment-related increase in tumor incidence was observed. In the reproduction study, no consistent pattern of effect from treatment between the F0 and F1 generation was seen in mating, pregnancy, or fertility indices. Thus, administration of PNA at levels which produced significant methemoglobinemia and low-level anemia in the rat and histological changes in the spleen produced no tumors or reproducible effects on reproductive performance.

This article reports the findings of a study analyzing the effects of rate setting on the financial condition of New York hospitals from 1974 to 1980. During this period, the New York rate review system was considered one of the most stringent--and successful--cost containment programs in the county. The conclusions of this study indicate that there may be serious long-term consequences of cost containment programs of this type.

Repeated inhalation exposure and 1-generation reproduction studies have been conducted in the rat to address the adequacy of the 10 ppm occupational exposure limit established for 1,2,3-trichloropropane (TriCP). Groups of 5 rats per sex were exposed for 6 h/d, 5 d/wk up to 4 wk to target TriCP concentrations of 0-900 ppm. Nine of 10 rats died after a single exposure at 900 ppm. Additional deaths were seen in the 300 (1 death) and 600 (3 deaths) ppm test groups. Mean body weights for all TriCP-treated groups were lower than control values. Liver weights were increased in animals of both sexes at 600 ppm and lower. For females ovary weights for the 300 and 600 ppm groups and spleen weights for the 300 ppm group were lower than those of controls. Males exhibited decreased testes weights only at the 600 ppm TriCP level (not evaluated at 900 ppm). Results of a 13-wk exposure, 6 h/d, 5 d/wk of 15 rats/sex.group to TriCP target vapor concentrations of 5, 15, or 50 ppm also resulted in liver weight increases at all test levels. Histopathologic examination showed hepatocellular hypertrophy in male rats at all TriCP levels. Other microscopic findings related to treatment in rats exposed to 15 ppm and to 5 ppm TriCP included lung hyperplasia (both sexes) and splenic extramedullary hematopoiesis (females only) and parallel observed organ weight increases. No treatment-related deaths were observed in this study, nor were there apparent effects on the hematology or clinical chemistries. Group mean body weights at 50 ppm (both sexes) and 15 ppm (females only) TriCP were reduced when compared to controls. In a 13-wk follow-up study in rats at 0, 0.5, and 1.5 ppm TriCP, no gross or microscopic findings related to treatment were found. Groups of 10 male and 20 female rats were exposed 6 h/d, 5 d/wk to 0, 5, or 15 ppm TriCP vapor during premating and mating. Females also were exposed during gestation. Low mating performance was observed in all groups of female rats including the controls, although fewer females in the 15-ppm group mated than in other study groups. Mating and fertility indices of male rats in both treated and control groups were generally low. All measured progeny indices appeared unaffected by treatment. A follow-up study of the same design was conducted at levels of 0, 0.5, and 1.5 ppm TriCP.(ABSTRACT TRUNCATED AT 250 WORDS)

Groups of 30 male and 30 female Sprague-Dawley CD rats, designated as the F0 generation, were exposed to vapor of monochlorobenzene (MCB) at target concentrations of 0, 50, 150, or 450 ppm for 10 weeks prior to mating and during mating, gestation, and lactation. The progeny of the F0 generation was designated as the F1 generation and groups of 30 male and 30 female F1 animals were exposed to the same concentrations of MCB as the F0 parents. Exposure of F1 animals was initiated 1 week postweaning and lasted 11 weeks prior to mating and through mating, gestation, and lactation. All F2 pups were observed through weaning at which time they were killed. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. No mortality was observed during the course of this study. Body weights and food consumption for all treated groups were comparable to controls during the growth period. Maternal body weight data during gestation and lactation were also comparable between the control and treated groups. Mating and fertility indices for males and females for both generations appeared unaffected by treatment. Pup and litter survival indices for all treated groups were comparable to those of controls. Hepatocellular hypertrophy and renal changes (tubular dilation with eosinophilic material, interstitial nephritis, and foci of regenerative epithelium) were observed among F0 and F1 male rats exposed to 150 and 450 ppm MCB.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was carried out to determine of patients enrolled in family practice clinics were satisfied with their care and to ascertain if there was a difference in the level of satisfaction between two groups of family practice patients: one group at a teaching medical center and the other at a general acute care community hospital. The overwhelming majority of family practice patients surveyed were extremely satisfied with the care they were receiving. The prime reasons for this satisfaction were physician continuity (having one physician for the whole family), personal attention, and having levels of satisfaction between the groups at a teaching and a non-teaching facility. Overall, families that had received preventive health instructions from their physician had a stronger desire to remain with family practice and had fewer dislikes about the program than did the group of patients who had not received any preventive health instructions from their physician.

Mated CD Sprague-Dawley rats and CD-1 mice were exposed during the period of organogenesis to target concentrations of 0, 250, 1000, and 2500 ppm methyl t-butyl ether (MTBE). None of the control or test-group animals died during the treatment or posttreatment periods. Females were sacrificed on d 20 (rats) or d 18 (mice). No adverse effects of treatment were reflected in maternal parameters of body weight, water consumption, or liver weight or in physical examination data for either species. Food consumption fell in the groups of treated rats during d 9-12; similar but nonsignificant effects were observed for mice during d 12-15. In rats, no treatment-related changes were recorded in the uterine implantation data, fetal size parameters, or fetal sex distribution data. Examination of fetuses for external abnormalities, skeletal malformations, or ossification variations did not reveal any changes caused by MTBE exposure. A slight increase in fetal resorptions was observed in the groups of mice exposed to low and high concentrations; this increase was attributed to two females in each group that had an unusually high number of resorptions, rather than to the treatment itself. No significant effects were observed in any groups of treated mice on external and soft-tissue examination or evaluation of skeletal abnormalities or ossification variations. The incidence of fused sternebrae in the high-concentration group increased slightly, which might be attributed to fetotoxicity.

Male rats exposed to target concentrations of methyl tertiary butyl ether (MtBE) at 300, 1300 and 3400 ppm for 6 hours/day, 5 days/week for 12 weeks were mated to female rats exposed to the same concentrations for a 3-week period. Exposures continued through the mating period and the females continued exposures during gestation and from days 5-21 lactation of the litters (F1a) (no exposures days 0-4 lactation). A second litter (F1b) was produced under the same mating and post mating exposure regimen. No adverse effect of treatment was observed with the adult animals (Fo) throughout the in-life portion of the study. The only remarkable finding was an increased incidence of dilated renal pelves in the low- and high-dose females (Fo). All gonad weights, male accessory reproductive organ weights, organ-to-body weight ratios and reproductive organ histopathology were unremarkable upon comparison of treated animals with air sham controls. The mating indices and fertility indices in exposed animals for both mating intervals (F1a and F1b) were not significantly different from controls. Pregnancy rates were comparable between treated and control females for the first litter interval (F1a) but were slightly lower (not statistically significant) than control on the second litter interval (F1b). Treated animal mean gestation length and the mean number of pups at birth were not statistically different from controls. The pup viability indices at birth were comparable for control and treated groups for the F1a generation, but the mid- and high-dose groups displayed a slight statistically significant decrease in the F1b generation; the decrease was not considered to be biologically significant and perhaps not treatment-related. Litter survival indices were comparable between control and treated groups for both litter intervals. Pups of mid- and high-dose females had slightly lower (not statistically significant) mean weights at days 14 and 21 of lactation but this was not considered treatment-related. The most frequent post-mortem observation for pups sacrificed at day 21 of lactation was dilated renal pelves. This did not appear to be related to treatment. It is concluded that MtBE inhalation in rats results in little adverse reproductive toxicity as shown in a two litter, one generation reproduction assay in rats.