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Trypanosoma cruzi is an important cause of disease and death in humans and dogs, and although wildlife infections are common, less is known about disease manifestations. A 12-week-old male American black bear (Ursus americanus) cub with mild lethargy and anorexia presented to a wildlife rehabilitation center in Lake Tahoe, California. The cub continued to become increasingly weak and showed decreasing interest in play and other activities. The cub was anemic and had increased γ-glutamyltransferase (GGT) liver enzymes. A large number of trypanosomes were noted on a thin blood smear. Trypanosoma cruzi was isolated in culture from a subsequent blood collection. Proliferative bony lesions were noted on radiographs, but this finding was considered unrelated to the T. cruzi infection. The number of parasites observed in thin blood smears dramatically dropped over time, but it remained PCR positive until at least nine months. The cub continued to gain weight and became increasingly active. Serum samples from the cub were positive with three different serologic assays (IFA, ELISA, and ICT). The bear was not treated because of the decreasing parasitemia and the improvement in activity and appetite. Although the bear could not be released due to issues unrelated to T. cruzi, it remains healthy in a captive facility. Sequence analysis of the DHFR-TS and COII-ND1 gene sequences confirmed the bear was infected with DTC TcIV. Following the detection of this clinical case, a serologic survey was conducted to determine the prevalence of T. cruzi exposure of black bears in California, North Carolina, and Pennsylvania. Because no serologic assay has been validated for use in bears, three different assays were used. Marked differences in apparent seroprevalence range from 1% (requiring all three assays to be positive) to ∼20.7% (requiring only one assay to be positive). Black bears are naturally exposed to T. cruzi across the United States. Future studies using PCR testing of tissues or blood would be needed to better understand the prevalence of T. cruzi in wild black bears, lineages most commonly associated with infection, and if T. cruzi represents a health threat to bears., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In 2021, the U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and state partners investigated a multistate sample-initiated retrospective outbreak investigation (SIROI) consisting of a cluster of nine Salmonella Weltevreden illnesses associated with frozen, precooked shrimp imported from India. Import surveillance testing identified Salmonella Weltevreden recovered from a cooked shrimp sample from Supplier B. In total, nine patients with clinical isolates highly related via whole genome sequencing were reported in four states with illness onset dates between February 26 and July 17, 2021. Epidemiologic data were gathered by state partners for seven patients, who all reported exposure to shrimp. Five patients reported consuming shrimp cocktail from the same retailer. A traceback investigation for five of the six patients converged on Supplier B. This evidence demonstrated that the outbreak of Salmonella Weltevreden illnesses was caused by the consumption of cooked, ready-to-eat shrimp manufactured by Supplier B. At the time of the investigation, outbreak and recall information was shared with Indian competent authorities. In March 2022, a follow-up inspection of Supplier B's facility in India was conducted, and insanitary conditions and practices were observed. This outbreak investigation highlighted the importance of multidisciplinary national and international public health partnerships. The lessons learned from this investigation should continue to inform investigational activities and food safety guidance for the industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Keeping the global food supply safe necessitates international collaborations between countries. Health and regulatory agencies routinely communicate during foodborne illness outbreaks, allowing partners to share investigational evidence. A 2016-2020 outbreak of Listeria monocytogenes infections linked to imported enoki mushrooms required a multinational collaborative investigation among the United States, Canada, Australia, and France. Ultimately, this outbreak included 48 ill people, 36 in the United States and 12 in Canada, and was linked to enoki mushrooms sourced from one manufacturer located in the Republic of Korea. Epidemiologic, laboratory, and traceback evidence led to multiple regulatory actions, including extensive voluntary recalls by three firms in the United States and one firm in Canada. In the United States and Canada, the Korean manufacturer was placed on import alert while other international partners provided information about their respective investigations and advised the public not to eat the recalled enoki mushrooms. The breadth of the geographic distribution of this outbreak emphasizes the global reach of the food industry. This investigation provides a powerful example of the impact of national and international coordination of efforts to respond to foodborne illness outbreaks and protect consumers. It also demonstrates the importance of fast international data sharing and collaboration in identifying and stopping foodborne outbreaks in the global community. Additionally, it is a meaningful example of the importance of food sampling, testing, and integration of sequencing results into surveillance databases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Superficial fibromatosis exhibits variable MR signal intensity due to collagenous and fibroproliferative components. Quantifying this signal heterogeneity using image texture analysis and T2-mapping could have prognostic and therapeutic implications., Methods: This IRB-approved retrospective study included 13 patients with superficial fibromatosis, managed by observation, electron beam radiotherapy (EBT), or pentoxifylline/vitamin E. Two-dimensional regions of interest (ROIs) were drawn on proton-density or T2-weighted MRI for radiomics feature analysis, and corresponding T2-maps. Comparisons were made between baseline and follow-up T2 relaxation times and radiomics features: Shannon's entropy, kurtosis, skewness, mean of positive pixels (MPP), and uniformity of distribution of positive gray-level pixel values (UPP)., Results: There were 19 nodules in 13 subjects. Mean patient age was 60 years; 62% (8/13) were female; mean follow-up was 9.7 months. Nodule diameter at baseline averaged 18.2 mm (std dev 16.2 mm) and decreased almost 10% to 16.6 mm (p = 0.1, paired t-test). Normalized T2 signal intensity decreased 23% from 0.71 to 0.55 (p = 0.03, paired t-test). T2 relaxation time decreased 16% from 46.5 to 39.1 ms (p < 0.001, paired t-test). Among radiomics features, skewness increased to 0.71 from 0.41 (p = 0.03, paired t-test), and entropy decreased from 8.37 to 8.03 (p = 0.05, paired t-test); differences in other radiomics features were not significant., Conclusions: Radiomics analysis and T2-mapping of superficial fibromatosis is feasible; robust decreases in absolute T2 relaxation time, and changes in image textural features (increased skewness and decreased entropy) offer novel imaging biomarkers of nodule collagenization and maturation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Scombrotoxin fish poisoning (SFP) is caused by the ingestion of certain fish species with elevated concentrations of histamine due to decomposition. In fall 2019, the U.S. Food and Drug Administration (FDA) was notified of 51 SFP cases including two hospitalizations from 11 states through the FDA consumer complaint system or directly from state partners. A case patient was defined as an individual who experienced a histamine-type reaction after consumption of tuna imported from Vietnam and an illness onset between 14 August and 24 November 2019. A traceback investigation was initiated at 19 points of service to identify a common tuna source. The FDA and state partners collected 34 product samples throughout the distribution chain, including from a case patient's home, points of service, distributors, and the port of entry. Samples were analyzed for histamine by sensory evaluation and/or chemical testing. Case patients reported exposure to tuna imported from Vietnam. The traceback investigation identified two Vietnamese manufacturers as the sources of the tuna. Twenty-nine samples were confirmed as decomposed by sensory evaluation and/or were positive for elevated histamine concentrations by chemical testing. Both Vietnamese companies were placed on an import alert. Seven U.S. companies and one Vietnamese company initiated voluntary recalls. The FDA released public communication naming the U.S. importers to help suppliers and distributors identify the product and effectuate the foreign company's recall. This SFP outbreak investigation highlights the complexities of the federal outbreak response, specifically related to imported food. Cultural considerations regarding imported foods should be addressed during outbreak responses when timing is critical. Collaboration with countries where confidentiality agreements are not in place can limit information sharing and the speed of public health responses., (Published 2021 by the International Association for Food Protection Not subject to U.S. Copyright.)

Introduction: Cancer sequencing efforts have revealed that cancer is the most complex and heterogeneous disease that affects humans. However, radiation therapy (RT), one of the most common cancer treatments, is prescribed on the basis of an empirical one-size-fits-all approach. We propose that the field of radiation oncology is operating under an outdated null hypothesis: that all patients are biologically similar and should uniformly respond to the same dose of radiation., Methods: We have previously developed the genomic-adjusted radiation dose, a method that accounts for biological heterogeneity and can be used to predict optimal RT dose for an individual patient. In this article, we use genomic-adjusted radiation dose to characterize the biological imprecision of one-size-fits-all RT dosing schemes that result in both over- and under-dosing for most patients treated with RT. To elucidate this inefficiency, and therefore the opportunity for improvement using a personalized dosing scheme, we develop a patient-specific competing hazards style mathematical model combining the canonical equations for tumor control probability and normal tissue complication probability. This model simultaneously optimizes tumor control and toxicity by personalizing RT dose using patient-specific genomics., Results: Using data from two prospectively collected cohorts of patients with NSCLC, we validate the competing hazards model by revealing that it predicts the results of RTOG 0617. We report how the failure of RTOG 0617 can be explained by the biological imprecision of empirical uniform dose escalation which results in 80% of patients being overexposed to normal tissue toxicity without potential tumor control benefit., Conclusions: Our data reveal a tapestry of radiosensitivity heterogeneity, provide a biological framework that explains the failure of empirical RT dose escalation, and quantify the opportunity to improve clinical outcomes in lung cancer by incorporating genomics into RT., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Drug resistant cancers like pancreatic ductal adenocarcinoma (PDAC) are difficult to treat, and nanoparticle drug delivery systems can overcome some of the limitations of conventional systemic chemotherapy. In this study, we demonstrate that FdUMP and dFdCMP, the bioactive, phosphorylated metabolites of the chemotherapy drugs 5-FU and gemcitabine, can be encapsulated into calcium phosphosilicate nanoparticles (CPSNPs). The non-phosphorylated drug analogs were not well encapsulated by CPSNPs, suggesting the phosphate modification is essential for effective encapsulation. In vitro proliferation assays, cell cycle analyses and/or thymidylate synthase inhibition assays verified that CPSNP-encapsulated phospho-drugs retained biological activity. Analysis of orthotopic tumors from mice treated systemically with tumor-targeted FdUMP-CPSNPs confirmed the in vivo up take of these particles by PDAC tumor cells and release of active drug cargos intracellularly. These findings demonstrate a novel methodology to efficiently encapsulate chemotherapeutic agents into the CPSNPs and to effectively deliver them to pancreatic tumor cells., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Until recently, hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrich syndrome (WAS). The first attempts at gene therapy for WAS using a ϒ-retroviral vector improved immunological parameters substantially but were complicated by acute leukemia as a result of insertional mutagenesis in a high proportion of patients. More recently, treatment of children with a state-of-the-art self-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit without inducing selection of clones harboring integrations near oncogenes. Here, we describe a case of a presplenectomized 30-year-old patient with severe WAS manifesting as cutaneous vasculitis, inflammatory arthropathy, intermittent polyclonal lymphoproliferation, and significant chronic kidney disease and requiring long-term immunosuppressive treatment. Following reduced-intensity conditioning, there was rapid engraftment and expansion of a polyclonal pool of transgene-positive functional T cells and sustained gene marking in myeloid and B-cell lineages up to 20 months of observation. The patient was able to discontinue immunosuppression and exogenous immunoglobulin support, with improvement in vasculitic disease and proinflammatory markers. Autologous gene therapy using a lentiviral vector is a viable strategy for adult WAS patients with severe chronic disease complications and for whom an allogeneic procedure could present an unacceptable risk. This trial was registered at www.clinicaltrials.gov as #NCT01347242., (© 2017 by The American Society of Hematology.)

Honey bees and other pollinators are exposed to fungicides that act by inhibiting fungal mitochondria. Here we test whether a common fungicide (Pristine®) inhibits the function of mitochondria of honeybees, and whether consumption of ecologically-realistic concentrations can cause negative effects on the mitochondria of flight muscles, or the capability for flight, as judged by CO2 emission rates and thorax temperatures during flight. Direct exposure of mitochondria to Pristine® levels above 5 ppm strongly inhibited mitochondrial oxidation rates in vitro. However, bees that consumed pollen containing Pristine® at ecologically-realistic concentrations (≈ 1 ppm) had normal flight CO2 emission rates and thorax temperatures. Mitochondria isolated from the flight muscles of the Pristine®-consuming bees had higher state 3 oxygen consumption rates than control bees, suggesting that possibly Pristine®-consumption caused compensatory changes in mitochondria. It is likely that the lack of a strong functional effect of Pristine®-consumption on flight performance and the in vitro function of flight muscle mitochondria results from maintenance of Pristine® levels in the flight muscles at much lower levels than occur in the food, probably due to metabolism and detoxification. As Pristine® has been shown to negatively affect feeding rates and protein digestion of honey bees, it is plausible that Pristine® consumption negatively affects gut wall function (where mitochondria may be exposed to higher concentrations of Pristine®)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Membrane proteins are attractive therapeutic targets, however the presence of detergents complicates biophysical binding measurements. Difficulties in determining quantitative dissociation constants for problematic membrane proteins were addressed by combining analytical ultracentrifugation and classical light scattering techniques. Validation of the algorithm used to calculate dissociation constants from sedimentation equilibrium experiments was demonstrated by analyzing binding data of the inhibitor Y-27632 to rho-kinase (ROCK). Kd's of 1.3 ± 0.7 and 52 ± 27 µM were calculated for ROCK constructs (S6-R415) and (M71-E379) respectively, consistent with previously published Ki's of 1.4 ± 0.1 and > 30 µM. Extension of the algorithm to membrane proteins required the collection of light scattering data to determine the partial specific volume, ν, for the membrane protein-detergent complex. Vitamin B12 binding to the bacterial protein btuB in octyl β-D-glucopyranoside (β-OG) illustrates the applicability of the method. A ν of 0.781 ml/g was determined for the btuB-β-OG complex. Incorporating this value into the algorithm generated a Kd of 7.0 ± 1.5 µM for the vitamin B12-btuB affinity. A Kd of 9.7 ± 2.7 µM was determined by equilibrium dialysis under similar experimental conditions. Successfully applying AUC to quantifying small-molecule ligand affinities to membrane proteins represents a significant advance to the field., (Copyright © 2011 Wiley-Liss, Inc.)

NK-cell leukemia is a clonal expansion of NK cells. The illness can occur in an aggressive or chronic form. We studied cell lines from human and rat NK-cell leukemias (aggressive NK-cell leukemia) as well as samples from patients with chronic NK-cell leukemia to investigate pathogenic mechanisms. Here we report that Mcl-1 was overexpressed in leukemic NK cells and that knockdown of Mcl-1 induced apoptosis in these leukemic cells. In vitro treatment of human and rat NK leukemia cells with FTY720 led to caspase-dependent apoptosis and decreased Mcl-1 expression in a time- and-dose-dependent manner. These biologic effects could be inhibited by blockade of reactive oxygen species generation and the lysosomal degradation pathway. Lipidomic analyses after FTY720 treatment demonstrated elevated levels of sphingosine, which mediated apoptosis of leukemic NK cells in vitro. Importantly, systemic administration of FTY720 induced complete remission in the syngeneic Fischer rat model of NK-cell leukemia. Therapeutic efficacy was associated with decreased expression of Mcl-1 in vivo. These data demonstrate that therapeutic benefit of FTY720 may result from both altered sphingolipid metabolism as well as enhanced degradation of a key component of survival signaling.

The chemical sector is confronted with risks pertaining to accidents involving dangerous substances. At the European level, a set of regulations - the Seveso regime - aims at controlling such risks. This article explores how this regime is put into practice, by analyzing the local practices of enforcement by Dutch inspectors and compliance by Dutch chemical companies. These empirical insights demonstrate that the classical 'positivistic risk paradigm' - which treats all risks as calculable, controllable and reducible - seems to dominate in the Seveso regime. The analysis in this article shows that this can lead to 'uncertainty blindness'; a regulatory regime where only yesterday's accidents are managed and salient future risks are potentially overlooked. We suggest that both regulators and regulated should start accepting the possibility of uncertain risks, which implies a cultural change in the current regulatory regime to 'uncertainty tolerance'., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: In 1989, Emory University initiated a linear accelerator (linac) radiosurgery program using circular collimators. In 2001, the program converted to a multileaf collimator. Since then, the treatment parameters of each patient have been stored in the record-and-verify system. Three major changes have occurred in the radiosurgery program in the past 6 years: in 2002, treatment was changed from static conformal beams to dynamic conformal arc (DCA) therapy, and all patients were imaged before treatment. Beginning in 2005, a linac was used, with the opportunity to treat at higher dose rates (600-1,000 monitor units/min). The aim of this study was to analyze the time required to deliver radiosurgery and the factors affecting treatment delivery. Benchmark data are provided for centers contemplating initiating linac radiosurgery programs., Materials and Methods: Custom software was developed to mine the record-and-verify system database and automatically perform a chart review on patients who underwent stereotactic radiosurgery from March 2001 to October 2006. The software extracted 510 patients who underwent stereotactic radiosurgery, and the following information was recorded for each patient: treatment technique, treatment time (from initiation of imaging, if done, to completion of therapy), number of isocenters, number of fields, total monitor units, and dose rate., Results: Of the 510 patients, 395 were treated with DCA therapy and 115 with static conformal beams. The average number of isocenters treated was 1.06 (range, 1-4). The average times to deliver treatment were 24.1 minutes for patients who underwent DCA therapy and 19.3 minutes for those treated with static conformal beams, reflecting the lack of imaging in the latter patients. Eighty percent of patients were treated in <30 minutes. For the patients who underwent DCA therapy, the times required to treat 1, 2, 3, and 4 isocenters were 23.9, 24.8, 33.1, and 37.8 minutes, respectively. Average beam-on time for these patients was 11.4 minutes. There has been no significant reduction in treatment delivery with the use of 1,000 monitor units/min, reflecting the fact that beam-on time is not the major determinant of overall treatment time., Conclusions: Multileaf collimator-based linac radiosurgery can be delivered efficiently in <30 minutes in the vast majority of patients. Given the limited treatment room utilization required for stereotactic radiosurgery treatments, this study calls into question the need for a dedicated radiosurgery unit for even busy treatment centers.

Objective: To determine the weight variation and calculated dosing variability of tablet fragments upon splitting unscored cyclobenzaprine hydrochloride 10 mg tablets using two common tablet splitting devices., Design: Comparative pharmaceutics study., Setting: Pharmacy school laboratory., Participants: Not applicable., Interventions: Unscored cyclobenzaprine hydrochloride 10 mg tablets from one generic manufacturer were split with a tablet splitter or a kitchen knife by a licensed pharmacist and two doctor of pharmacy students (n = 15 tablets for each method per participant)., Main Outcome Measures: Fragment weights (FWs) were compared with the theoretical weights (TWs), which were calculated as one half of the mean weight of the tablets used in each part of the experiment; means, relative standard deviations (RSDs), and percentages of TW were also calculated., Results: The mean weight before splitting the 45 tablets with the tablet splitter was 136.6 +/- 2.1 mg (TW = 68.3 mg). The mean FW after splitting was 67.9 +/- 7.9 mg. The RSD of 11.6% corresponded to a range of 69.4% to 130.2% of the TW and an estimated drug content of the split fragments between 3.47 mg and 6.51 mg. The mean weight before splitting the 45 tablets cut with a kitchen knife was 136.6 +/- 2.0 mg (TW = 68.3 mg). The mean FW was 68.0 +/- 15.7 mg with a RSD of 23.2%, corresponding to a range of 49.9% to 149.5% of the TW and an estimated drug content of the split fragments between 2.49 mg and 7.48, Conclusion: Tablet fragments obtained after splitting this generic cyclobenzaprine 10 mg product varied considerably in weight and estimated drug content. Accordingly, splitting cyclobenzaprine 10 mg tablets to achieve 5 mg doses could result in unpredictable dosing and therapeutic response.

Background: Peptide inhibitors of caspases have helped define the role of these cysteine proteases in biology. Structural and biochemical characterization of the caspase enzymes may contribute to the development of new drugs for the treatment of caspase-mediated inflammation and apoptosis., Results: The crystal structure of the previously unpublished caspase-7 (Csp7; 2.35 A) bound to the reversible tetrapeptide aldehyde inhibitor acetyl-Asp-Glu-Val-Asp-CHO is compared with crystal structures of caspases-1 (2.3 A), -3 (2.2 A), and -8 (2.65 A) bound to the same inhibitor. Csp7 is a close homolog of caspase-3 (Csp3), and these two caspases possess some quarternary structural characteristics that support their unique role among the caspase family. However, although Csp3 and Csp7 are quite similar overall, they were found to have a significantly different substitution pattern of amino acids in and around the S4-binding site., Conclusions: These structures span all three caspase subgroups, and provide a basis for inferring substrate and inhibitor binding, as well as selectivity for the entire caspase family. This information will influence the design of selective caspase inhibitors to further elucidate the role of caspases in biology and hopefully lead to the design of therapeutic agents to treat caspase-mediated diseases, such as rheumatoid arthritis, certain neurogenerative diseases and stroke.

Hydroponically grown wheat was intrinsically labelled with the stable isotope 106cadmium (106Cd) and the flour made into a porridge. The abundance of the isotope in the porridge was approximately 30 times the natural abundance, but the total level of Cd in the porridge was 0.03 mg/kg fresh weight, which was the same as expected in a normal diet. Cadmium measurements were made using inductively coupled plasma-mass spectrometry (ICP-MS). The porridge was eaten at breakfast by adult and infant volunteers. Bulked faecal collections were analysed for unabsorbed Cd. Initial results suggest that the apparent absorption of Cd may be higher than 5% as commonly quoted, but longer faecal collection times may be necessary to confirm this.

The permeable reactive barrier technology for in situ treatment of chlorinated solvents and other groundwater contaminants is becoming increasingly popular. Field scale implementation of this and other in situ technologies requires careful design based on the site-specific hydrogeology and contaminant plume characteristics. Groundwater flow modeling is an important tool in understanding the hydraulic behavior of the site and optimizing the reactive barrier design. A combination of groundwater flow modeling and particle tracking techniques was used to illustrate the effect of hydraulic conductivity of the aquifer and reactive media on key permeable barrier design parameters, such as the capture zone width, residence time, flow velocity, and discharge. Similar techniques were used to illustrate the modeling approach for design of different configurations of reactive barriers in homogeneous and heterogeneous settings.

The bioavailability of iron glycine added to a vegetable infant weaning food was compared with ferrous sulfate. Stable, isotopically labeled compounds (57Fe or 58Fe) were mixed into the midday meal (1.4 mg added Fe/serving) and fed to 9-mo-old infants on alternate days for 8 d. Bioavailability, expressed as a percentage of the dose consumed, was measured from isotopic enrichment of hemoglobin 14 d after the last test meal. There was no difference between iron glycine and ferrous sulfate (x+/-SEM): 9.0+/-0.7% and 9.9+/-0.8%, respectively. The effect of chelation was examined by measuring iron bioavailability of iron glycine and ferrous sulfate added to a high-phytate (310 mg/100 g) whole-grain cereal weaning food and comparing it with a lower-phytate (147 mg/100 g) vegetable food, as used in the first study. Both iron compounds had lower bioavailability from the high-phytate food, 5.2+/-0.5% for iron glycine and 3.8+/-0.9% for ferrous sulfate, than the lower-phytate food, 9.8+/-1.5% for iron glycine and 9.1+/-1.3% for ferrous sulfate. The results showed no significant difference in bioavailability between the two forms of iron when added to infant weaning foods, suggesting that the glycine complex was fully or partially dissociated in the gastrointestinal tract. It is concluded that chelation does not improve the bioavailability of iron in the presence of dietary inhibitors.

The effect of fortification iron (reduced iron) on zinc absorption from a commercial vegetable-based weaning food was assessed in 11 9-mo-old infants. Each infant was fed a test meal of unfortified or iron-fortified product, labeled extrinsically with 1 mg 67Zn or 70Zn (as citrate), and the next day was fed the second product labeled with the other isotope. A complete fecal collection was carried out for 3-4 d, and the amount of unabsorbed isotope measured by thermal-ionization quadrupole mass spectrometry. Apparent zinc absorption (isotope intake minus fecal excretion, expressed as the % of dose administered) was 31.1 +/- 8.3% (x +/- SD) from the iron-fortified food and 28.6%28.6 +/- 10.5% from the unfortified food. These values were not significantly different, thus iron fortification of the weaning food did not reduce zinc absorption.

The mouse liver is a frequent target organ for chemical carcinogenesis (Huff et al., 1988, 1991; Gold et al., 1989) and tumor development exhibits preferential strain sensitivity (Dragani et al., 1992; Drinkwater and Bennett, 1991). In some reports a positive correlation has been observed between the degree of spontaneous liver tumor incidence and the propensity to develop liver tumors after treatment with chemical carcinogens (Della Porta et al., 1967; Flaks, 1968; Dragani et al., 1984, 1987; Diwan et al., 1986; Drinkwater and Ginsler, 1986), but this is not always the case (Grasso and Hardy, 1975; Hanigan et al., 1988; Dragani et al., 1992). Thus, the interpretation of this endpoint in assessing potential health hazards to humans continues to be the subject of active debate. Studies of molecular and genetic factors that modulate the genesis of mouse liver tumors should enhance our understanding of the relevance of this response following exposure to genotoxic as well as nongenotoxic chemicals. To utilize intelligently animal models as surrogates for human carcinogenesis, the validity of rodent tumor endpoints in assessing potential human health hazards from chemical exposure remains an important issue. One approach has been to understand the animal system itself and the mechanisms by which chemicals induce tumors in the animal model. Information regarding the molecular events associated with tumor induction should make the relevance of results from rodent carcinogenicity studies to human risk easier to assess. Results to date have identified activation of ras proto-oncogenes as one early event and an important factor associated with chemical induction of mouse liver neoplasia (Reynolds et al., 1986, 1987; Wiseman et al., 1986), although ras-independent pathways appear to account for an appreciable proportion of some chemically induced mouse liver tumors (Fox et al., 1990; Buchmann et al., 1991). Available data emphasize the complexity of H-ras activation in murine hepatocarcinogenesis. Not only the genetic background of the mouse but also the dose of the carcinogen may influence significantly the number of tumors containing activated H-ras. Both high sensitivity and low sensitivity strains of mice can develop liver tumors which contain activated H-ras oncogenes, showing that the ability to activate this gene does not in itself determine susceptibility to hepatocarcinogenesis. Ras gene mutational profiles in chemically induced liver tumors may be different and distinguishable from those in spontaneous tumors. Since multiple genetic as well as nongenetic events are associated with tumor development, defining a precise role for ras gene mutations when they occur in mouse liver tumors is often difficult.(ABSTRACT TRUNCATED AT 400 WORDS)

The use of extrinsic stable and radioisotopic labels (Fe, Zn, Cu and Se) was compared with the use of intrinsic labels by measuring label retention in rats. Saccharomyces cerevisiae (Hansen strain CBS 1171) was prepared intrinsically enriched with a stable isotope of iron, zinc, copper or selenium, and unenriched freeze-dried yeast was extrinsically labeled with the appropriate stable and/or radioisotope. Male Wistar rats, weighing 80-100 g and fed a purified diet, were given a test meal of one of the above labeled yeasts. Isotopic retention was determined by fecal monitoring. Retention of the stable isotopes was determined by thermal ionization quadruple mass spectrometry (TIQMS) and retention of the radioisotopes by counting feces in a whole-body counter. The results indicated that the behavior of the labels differed among the minerals, with copper as the only one in which the intrinsic and extrinsic stable isotopes were comparably retained. With zinc, retention of the extrinsic radiolabel and intrinsic label was similar, but retention of the extrinsic stable isotope label was higher. With iron, the intrinsic label had a significantly lower retention than the two extrinsic labels; with selenium, retention of all three labels was different, but these differences were not of a sufficient magnitude to conclude that extrinsic stable isotopic labelling is not valid. These results demonstrate that an extrinsic stable isotope label can be used for copper, selenium and inorganic iron, but that such a label is not valid for studies on zinc.

The use of telephone surveys has increased significantly in the past decade. One advantage of telephone surveys is the ability to reach a large number of individuals: 97% of the US population owns telephones. Another advantage is cost savings: telephone surveys cost as little as one quarter to one half the amount of face-to-face surveys. Computer-assisted telephone interviewing has improved data collection, coding, and analysis. Random-digit dialing and a number of statistical advances such as weighting and stratification have significantly enhanced sample selection and research design of telephone surveys. The increasing need to collect dietary information from populations in an affordable fashion has expanded the use of telephone dietary surveys. To date, telephone dietary surveys have been used for follow-up after initial face-to-face contact has been made. The most common dietary instruments used are the 24-hour recall and the food frequency questionnaire. This review indicates that well-designed and well-administered telephone surveys are as good as, and may be better than, other methods for obtaining dietary information.

An awareness by health professionals of changing priorities facing the School Health Service (SHS) has led to increased attempts to evaluate current practice. In the present study we set out to examine how schools perceive the SHS, to identify their concerns and obtain their suggestions for improvements. Despite direct and repeated personal communication, only 26 questionnaires were returned out of 64 sent to primary and post primary schools. The majority of responses indicated a lack of knowledge about the various aspects of the SHS and a request for more information. Half the questionnaires indicated dissatisfaction with the current SHS--particular problems identified were poor communication, lack of information and inability to deal with social problems. Suggestions made by schools to improve the SHS include improved communication between schools, SHS and parents, better and increased health education. Schools identified the current health needs of pupils as health education; social, family and behavioural problems; and developmental problems. Overall those schools who responded welcomed the approach from the SHS.

Petrifilm ™ Yeast and Mold (YM) plates were compared to acidified potato dextrose agar (APDA) and chloramphenicol-supplemented plate count agar (CPCA) for its suitability to enumerate yeasts and molds in 13 groups of food products. These products consisted of beans (dry and frozen, green), corn meal, flour (wheat), fruit (apple), a meat/vegetable entree (chicken pot pie), a precooked meat (beef), milk (dehydrated, nonfat), nuts (pecans), pasta, potatoes (dehydrated), precooked sausage, and a spice (black pepper). Correlation coefficients of Petrifilm ™ YM plates versus APDA and CPCA pour plates for recovering total yeasts and molds from a composite of the thirteen test foods were, respectively, 0.961 and 0.974. Individually, Petrifilm™ YM plate counts were equivalent or higher than APDA and CPCA for some food groups and lower for other food groups. Because food particle interference can make enumeration of yeast and mold colonies on Petrifilm ™ YM plates difficult for some food groups, potential food interference will need to be evaluated for each food group tested.

The Petrifilm ™ Yeast and Mold (YM) plate was compared to acidified potato dextrose agar (APDA) and chloramphenicol-supplemented plate count agar (CPCA) using pour- and surface-plating techniques for its ability to recover yeasts and molds from hard and soft cheeses, cottage cheese, yogurt, sour cream, fruit juice, salad dressing, relishes, and tomato-based sauces. Correlation coefficients of Petrifilm ™ YM plates versus pour-APDA, surface-APDA, pour-CPCA, and surface-CPCA for recovering total yeasts and molds from a composite of the eight test foods were, respectively, 0.993, 0.993, 0.994, and 0.995. Slope and intercept values for populations detected using Petrifilm ™ YM plates versus traditional systems ranged, respectively, from 0.984 to 1.008 and -0.051 to 0.149. The coefficient of variation for total yeast and mold populations recovered on Petrifilm ™ YM plates was 1.0% compared to 1.2 to 1.7% for traditional enumeration systems. Regardless of the enumeration system employed or the type of fungal cell, i.e., yeast or mold, being enumerated, significantly (P ≤ 0.05) higher populations were generally detected after 5 d compared to 3 d of incubation. After 5 d of incubation, in no case were yeast or total yeast and mold populations detected in the eight food products using Petrifilm ™ YM plates significantly lower than respective populations detected using traditional pour- and surface-plating techniques and media. When Petrifilm ™ YM plates were used, significantly higher total yeast and mold populations were detected in 3, 1, and 1 out of eight food products compared to using, respectively, pour-APDA, surface-APDA, and surface-CPCA enumeration systems. The Petrifilm ™ YM plate offers an acceptable alternative to traditional methods for enumerating yeasts and molds in the dairy and high-acid products evaluated in this study.

Diet was measured by 5-day weighed inventory to search for an association between fat intake in the general population and factor VII coagulant activity (VIIc), a strong predictor of coronary heart disease. Of 275 men aged 40-59 years registered with a medical practice, 203 (74%) participated and 170 (62%) provided a satisfactory record. After allowance for the increase in fat intake with body size, a statistically significant and positive association was found between dietary fat and VIIc (r = 0.18; P less than 0.05). The correlation coefficient was increased to 0.24 when adjusted for the effect of day-to-day variability in individual fat intake, thereby providing an improved estimate of the true strength of association. The mean difference in VIIc of 12% of standard between men in the highest and lowest quarters of the distribution of fat intake was similar to that reported between men experiencing coronary heart disease and those remaining free. The results support previous experimental fat-feeding studies and suggest that a high fat diet has adverse consequences for blood coagulability and coronary thrombosis.

The nuclear amber mutation, pet494-1, specifically blocks the accumulation of the product of the mitochondrial gene oxi2, cytochrome oxidase subunit III. The pet494-1 mutation does not prevent transcription of the mitochondrial gene since RNA--gel blot hybridizations showed that mutant cells contain normal amounts of an oxi2 transcript, indistinguishable in size from wild-type. A mitochondrial mutation that partially suppresses the nuclear mutation was isolated. The "mitochondrial revertant" behaved as though it contained two different mitochondrial DNAs: one rho+, the other rho-. The suppressor mutation is carried on the rho- mitochondrial DNA and is apparently the result of a gene fusion between oxi2 and another mitochondrial gene, oxi3. This gene rearrangement replaced the normal 5'-non-translated sequence of oxi2 with a portion of the open reading frame of the second intron of oxi3. Novel transcripts of the rearranged gene, containing oxi3 sequences upstream from oxi2 were detected in the mitochondrial revertant. The strain accumulated an electrophoretically variant form of cytochrome oxidase subunit III, probably translated from a new initiation codon. The data are consistent with models in which the PET494 protein acts within the mitochondria to specifically promote the translation of the oxi2 messenger RNA.

Adult White Plymouth Rock hens were submitted to a heat shock of 42.2 C. It was demonstrated that .1% thiouracil fed for 4 weeks prior to heat stress significantly increased survival time. Administration of DL-thyroxine administered at the rate of 4 micrograms/100 g body weight injected on day of testing did not alter survival time. However, survival under heat shock was significantly reduced if DL-thyroxine was administered daily for 3 days prior to testing. White Rocks exhibited significantly longer survival time under heat shock than Single Comb White Leghorns, and females of both breeds exhibited significantly longer survival time their male counterparts. Treatment with DL-thyroxine greatly reduced the survival time differences between breeds and sex. The implications of these findings for applied breeding programs are discussed.

Ninety vanilla frozen dessert mix samples were analyzed to determine total microbial populations and coliforms present in samples inoculated with a coliform isolated from raw milk. Standard methods agar (SMA, PCA, Difco) and violet red bile agar (VRBA, Difco) as well as Petrifilm™ (PSM, PVRB) were used for plating of samples. Standard VRBA 1:10 method produced significantly higher counts of colony-forming units (CFU) than PVRB 2:3 and VRBA 2:3 methods. VRBA 2:3 colony-forming unit counts were also significantly higher than those on PVRB 2:3, but both methods showed a moderately strong linear relationship. Repeatabilities of all three coliform plating methods (VRBA 1:10, VRBA 2:3, and PVRB 2:3) were acceptably low. Less than 10% of samples plated on SMA and PSM resulted in total aerobic colony-forming units in the countable range, making evaluation of data difficult and resulting in a lack of strong linear relationship between PSM and SMA. An additional 70 local retail store samples containing naturally occurring coliforms were evaluated using PVRB 2:3 and VRBA 1:10 methodology, confirmed in brilliant green lactose bile broth (BGLB, Difco) and compared to standard VRBA 1:10 previously analyzed. All methods were equivalent for mean log coliforms, i.e., 1.38,1.33, and 1.31 for PVRB 2:3, VRBA 2:3, and VRBA 1:10, respectively. Petrifilm™ methods were comparable to standard methods for enumerating coliforms in frozen dairy products, and would be a valid alternative to standard coliform and total plate count methods.

Since approximately 1% of 3-ketosteroid reductase (which metabolizes dihydrotestosterone (17 beta-hydroxyl-5 alpha-androstan-3-one] to 5 alpha-androstane-3 alpha, 17 beta-diol or 5 alpha-androstane-3 beta, 17 beta-diol) from mouse kidney cytosol adheres to DNA under conditions that allow virtually complete androgen receptor binding, these two DNA-binding activities were compared in cytosol extracts of mouse kidney and hypothalamus-preoptic area. This DNA-binding fractions of 3-ketosteroid reductase was distinguished from androgen receptor in several ways: (1) its pattern of elution from DNA-cellulose with steps of increasing NaCl concentration differed from that for receptors from wild-type kidney; (2) it was influenced differently by the mutation Tfm, both in level and in DNA-cellulose elution pattern; (3) in mouse kidney cytosol it was relatively stable at moderate (25 degrees C) temperatures which rapidly inactivated ligand-free androgen receptors in the same cytosols; (4) the DNA-binding was not proportional to androgen receptor levels between two wild-type tissues, the hypothalamus-preoptic area and kidney. By these criteria, a simple relationship of androgen receptors and a DNA-binding fraction of 3-ketosteroid reductase activity is unlikely.

Rutgers Medical School was started in 1962 as a two year medical school. By 1976 its basic science enrollment had grown to 108 and it retained 56 students each year for clinical instruction. During the early 1970's the medical school had been frustrated on three different occasions in its attempts to build an on-campus teaching hospital. This paper describes the school's successful post-1976 planning efforts to provides its faculty and students with the appropriate clinical facilities by a model which would generate support among external constituencies. The history of the medical school prior to 1976 is presented briefly. The paper then develops the rationale for the new planning model and shows the relationship of the model to the educational bases of the institution. It then tracks the planning process from program development through approvals by the external constituencies and brings the school's experience to the present where ¿ million dollars of construction is under contract for health care delivery and medical education facilities.

Previous studies from this laboratory have demonstrated a relationship between the C+ and c alleles at the recessive white locus and body weight at 8 and 26 weeks of age. Similar studies have been conducted on the same randombred population 20 and 21 generations later. In addition, one experiment involved a comparison of colored and recessive white birds when grown on a low energy replacement starter vs. a high energy broiler starter. The 1981 progeny studied were produced by 100 females housed in single bird cages and inseminated with pooled semen from 20 males. The gene frequency for the recessive white gene (c) was .56 +/- .023 and the recessive white segregates were approximately 35% of the progeny produced. The 8-week body weights of the recessive white progeny as a percentage of the colored phenotype (C+/-) was 88.8% for males and 92.5% for females. These body weight differences at 8 weeks were highly significant (P less than .005). The recessive white genotype also reduced 26-week body weight of females and 38-week egg weight. As expected, there were highly significant differences (P less than .001) in body weight at 4, 6, and 8 weeks of age due to rations. However, there was no evidence of a genotype X ration interaction. The observed differences between genotypes (C+/- vs. c/c) were similar regardless of the energy level of the ration. These results confirm and extend the earlier observations on the depressing effect of the recessive white genotype on early growth and support the conclusion that this relationship represents a pleiotropic effect of the gene and is not the result of linkage disequilibrium.

The 3M Company has developed a sample-ready system (Petrifilm ™ SM) for enumerating bacteria in milk and other food products. The testing unit consists of Standard Methods culture medium coated onto a base film and overlaid with a second film coated with a cold-water-soluble gelling agent and tetrazolium indicator dye. As such, the system is ready to accept samples of product. A pipette or 0.001-ml plate loop continuous pipetting syringe can be used for applying samples. In this study, both methods of sample addition were used and results compared with those of the Standard Plate Count (SPC) and standard Plate Loop (PL) methods for determining bacteria numbers in raw milk. In total, 108 samples were analyzed in duplicate by each of the four methods. The correlation coefficients (r) between the 3M-SPC and SPC, 3M-PL and PL, 3M-PL and SPC and PL and SPC were 0.946, 0.935, 0.941, and 0.974, respectively. Repeatability, as measured by mean log 10 variance for duplicate determinations, was essentially the same for the four methods, and in all instances less than 0.005. The mean log 10 differences between the SPC and 3M-SPC, and SPC and 3M-PL were, respectively, -0.177 and -0.168. The preceding statistical criteria suggest the Petrifilm™ SM method to be a suitable alternative to the SPC or the PL procedure.

Studies were conducted on the effects of the columbian restriction gene, Co, on early growth rate in the domestic fowl. There were no statistically significant effects of the Co gene on body weights at 4, 6, and 8 weeks of age. The importance of these findings is discussed in relationship to the desired presence of the Co gene to enhance sex identification in sex-linked crosses utilizing the silver (S) and gold (s+) alleles.

Petrifilm ™ methods were compared to traditional plating methods for monitoring microbial contamination in poultry processing facilities. No differences were seen between the Petrifilm methods and conventional method for enumeration of total bacterial populations, and no trends were seen in the ability of either method to detect coliforms in naturally contaminated samples. When processed poultry products were artificially inoculated with a variety of microorganisms, no difference in efficiency of recovery of the bacteria was noted. The Petrifilm methods were shown to be a practical and accurate alternative for monitoring microbial levels in poultry processing facilities.

Experiments were conducted to study the regulation of the developmental pattern of aromatase in the forebrain of the perinatal rat. Two experimental designs were used: aromatase measured in primary cultures of fetal hypothalamic cells and in cell-free preparations of forebrain tissue excised at varying ages. In cultured cells, aromatase decreased logarithmically at a slow rate (t1/2 = 7.8 days). Norepinephrine caused a pronounced dose (4 x 10(-6) M) and time-dependent (2-6 days) drop in aromatase without affecting the levels of 5 alpha-reductase or substance P. In isolated tissue, aromatase activity was compared with the concentrations of norepinephrine and dopamine in the forebrain of males vs females at different perinatal ages and in discrete forebrain areas at postnatal day 4. In no case was a sex difference in catecholamines seen. An overall developmental decline in aromatase was associated with developmental increases in catecholamine levels. Acute treatment with the beta-agonist, isoproterenol, had no effect on brain aromatase activity.