Perceptions of emergency medicine residents on the quality of residency training in the United States and Saudi Arabia / 世界急诊医学杂志（英文）

BACKGROUND:We compare educational environments (i.e. physical, emotional and intel ectual experiences) of emergency medicine (EM) residents training in the United States of America (USA) and Saudi Arabia (SA). METHODS:A cross-sectional survey study was conducted using an adapted version of the validated Postgraduate Hospital Educational Environment Measure (PHEEM) survey instrument from April 2015 through June 2016 to compare educational environments in all emergency medicine residency programs in SA and three selected programs in the USA with a history of training Saudi physicians. Overall scores were compared across programs, and for subscales (autonomy, teaching, and social Support), using chi-squared, t-tests, and analysis of variance. RESULTS:A total of 219 surveys were returned for 260 residents across six programs (3 SA, 3 USA), with a response rate of 84％. Program-specific response rates varied from 79％–100％. All six residencies were qualitatively rated as "more positive than negative but room for improvement". Quantitative PHEEM scores for the USA programs were significantly higher:118.7 compared to 109.9 for SA, P=0.001. In subscales, perceptions of social support were not different between the two countries (P=0.243); however, role autonomy (P<0.001) and teaching (P=0.005) were better in USA programs. There were no significant differences by post-graduate training year. CONCLUSION:EM residents in all three emergency medicine residency programs in SA and the three USA programs studied perceive their training as high quality in general, but with room for improvements. USA residency programs scored higher in overall quality. This was driven by more favorable perceptions of role autonomy and teaching. Understanding how residents perceive their programs may help drive targeted quality improvement efforts.

A comparison of perspectives on costs in emergency care among emergency department patients and residents / 世界急诊医学杂志（英文）

@#BACKGROUND: Costs of care are increasingly important in healthcare policy and, more recently, in clinical care in the emergency department (ED). We compare ED resident and patient perspectives surrounding costs in emergency care. METHODS: We conducted a mixed methods study using surveys and qualitative interviews at a single, academic ED in the United States. The two study populations were a convenience sample of adult ED patients (>17 years of age) and ED residents training at the same institution. Participants answered open- and closed-ended questions on costs, medical decision making, cost-related compliance, and communication about costs. Closed-ended data were tabulated and described using standard statistics while open-ended responses were analyzed using grounded theory. RESULTS: Thirty ED patients and 24 ED residents participated in the study. Both patients and residents generally did not have knowledge of medical costs. Patients were comfortable discussing costs while residents were less comfortable. Residents agreed that doctors should consider costs when making medical decisions whereas patients somewhat disagreed. Additionally, residents generally took costs into consideration during clinical decision-making, yet nearly all residents agreed that they had too little education on costs. CONCLUSION: There were several notable differences in ED patient and resident perspectives on costs in this U.S. sample. While patients somewhat disagree that cost should factor into decision making, generally they are comfortable discussing costs yet report having insufficient knowledge of what care costs. Conversely, ED residents view costs as important and agree that cost should factor into decision making but lack education on what emergency care costs.

Microclimatic conditions and their effects on sheep behavior during a live export shipment from Australia to the Middle East.

The microclimate can potentially impact the health and welfare of livestock exported by ship. Within-pen microclimatic conditions were recorded and the effects of ammonia on sheep behavior investigated on a voyage from Australia to the Middle East. Ammonia, carbon dioxide, and hydrogen sulfide as well as wet-bulb, dry-bulb, and dew-point temperature and air speed were mapped in 20 open-deck focal pens, with the focus on the behavior and location of a marked sheep in each pen. Air speed was highly variable in most pens, with pockets of high but transient concentrations of ammonia (30.7 to 44.2 mg/m(3)) in 20% of pens that had no or minimal air flow. Carbon dioxide concentrations varied in some pens, but overall concentrations of carbon dioxide and hydrogen sulfide were low. Sheep in pens previously identified to have high ammonia concentrations, high wet-bulb temperatures, and low wind speed stood longer (P = 0.003) and spent less time feeding (P = 0.01) and ruminating (P = 0.004) than those in pens previously identified with low ammonia, low wet-bulb temperature, and high wind speed. Moreover, sheep exposed to increased ammonia concentrations held their head higher (P = 0.004) to avoid the greater ammonia concentrations at lower heights, and these sheep had more conjunctivitis (P < 0.001). Sheep movement around the pen was limited. Increased time spent lying down (P = 0.04) and more rhythmical behavior in the second half of the voyage indicated that the sheep adjusted to shipboard conditions over time. It is concluded that high, transient concentrations of ammonia existed in some pens, which adversely affected the behavior of sheep.

Effect of an 8.0% arginine and calcium carbonate desensitizing toothpaste on shear dentin bond strength.

OBJECTIVE: The objective of this study was to determine the effect of an 8.0% arginine and calcium carbonate desensitizing toothpaste (Colgate Sensitive Pro-Relief) on shear bond strength of composites to bovine incisor dentin. METHODS: Bovine incisors were sectioned and prepared into 27 dentin specimens. The experimental group had 13 specimens treated for 10 sessions of two-minute brushing with an 8.0% arginine and calcium carbonate desensitizing toothpaste, followed by a 30-second agitated water wash. The control group had 14 specimens treated with flour of pumice only. Each specimen was dried, etched with 35% phosphoric acid for 15 seconds, and washed clean. A bonding agent was applied and polymerized. A 2.38 mm diameter column of Filtek Supreme A2 was bonded to the surface and polymerized as per manufacturer's instructions. Specimens were stored in water for at least 48 hours, subjected to a shear force at a crosshead speed of 0.5 mm/minute on an Instron mechanical testing device, and force at failure was recorded. A one-sided t-test was used to evaluate significant differences among the groups as measured by mean shear strength. RESULTS: Mean shear force was 19.6 +/- 9.4 (SD) for the experimental group and 15.4 +/- 6.0 for the control group with p = 0.0291. CONCLUSION: No significant differences were found for bond strength to dentin treated with an 8.0% arginine and calcium carbonate desensitizing toothpaste or pumice. Dentists can still achieve optimal dentin bonding results if a patient is using Colgate Sensitive Pro-Relief to manage dentin hypersensitivity.

The effect of inhibition of heat-shock proteins on thiram-induced tibial dyschondroplasia.

Tibial dyschondroplasia (TD) is a skeletal abnormality that can cause economic losses and animal welfare concerns. Thiram-induced TD is characterized by enlarged, unvascularized growth plates, low levels of the vascular endothelial growth factor receptor Flk-1, abnormal chondrocyte differentiation, and lameness. Recently we reported the involvement of heat-shock protein 90 (Hsp90) in chondrocyte differentiation and growth-plate vascularization. Inhibition of Hsp90 activity in thiram-induced TD resulted in increased Flk-1 levels, re-instated normal growth-plate angiogenesis and morphology, and abrogated lameness. In the present study, we evaluated the efficacy of various concentrations of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90 activity, in preventing growth-plate histopathology and lameness in TD-affected chicks. Low doses of 17-DMAG (2 injections, each of 100 or 300 µg) did not prevent TD development even though Flk-1 levels were restored, which suggests that Flk-1 is not the only rate-limiting factor in growth-plate angiogenesis. High doses of 17-DMAG (2 injections, each of 600 or 900 µg) prevented BW loss, decreased the TD score, reduced lesion width, restored proper chondrocyte differentiation, increased blood vessel invasion, and eliminated lameness. To assess the specificity of Hsp90, we evaluated the efficacy of the flavonoid quercetin, an inhibitor of Hsp70 synthesis, in preventing TD development; it decreased Hsp70 levels but not those of Hsp90 in the control growth plates and prevented upregulation of Hsp70 in the TD-affected growth plates. Dietary quercetin (at 100 or 500 ppm) did not prevent the hypoxia that is characteristic of the TD-affected growth plate or development of thiram-induced TD and lameness. The present results demonstrate the specificity and the major role of Hsp90 in chondrocyte differentiation and growth-plate vascularization. In contrast to the anti-angiogenic effect of 17-DMAG observed in mammals, inhibition of Hsp90 activity in the unvascularized TD-affected growth plates resulted in activation of the angiogenic switch and restored normal growth-plate morphology.

Physiological and behavioral responses of sheep to gaseous ammonia.

Ammonia can accumulate in highly stocked sheep accommodation, for example during live export shipments, and could affect sheep health and welfare. Thus, the objective of this experiment was to test the effects of 4 NH(3) concentrations, 4 (control), 12, 21, and 34 mg/m(3), on the physiology and behavior of wether sheep. Sheep were held for 12 d under a micro-climate and stocking density similar to shipboard conditions recorded on voyages from Australia to the Middle East during the northern hemispheric summer. Ammonia increased macrophage activity in transtracheal aspirations, indicating active pulmonary inflammation; however, it had no effect (P > 0.05) on hematological variables. Feed intake decreased (P = 0.002) in proportion to ammonia concentration, and BW gain decreased (P < 0.001) at the 2 greatest concentrations. Exposure to ammonia increased (P = 0.03) the frequency of sneezing, and at the greatest ammonia concentration, sheep were less active, with less locomotion, pawing, and panting. Twenty-eight days after exposure to NH(3), the pulmonary macrophage activity and BW of the sheep returned to that of sheep exposed to only 4 mg/m(3). It was concluded that NH(3) induced a temporary inflammatory response of the respiratory system and reduced BW gain, which together indicated a transitory adverse effect on the welfare of sheep.

Accumulation of ammonia and other potentially noxious gases on live export shipments from Australia to the Middle East.

Noxious gases on ships are irritant pollutants that have potential impacts on the comfort and health of both livestock and humans. Identification of environmental influences on the pollutants will assist live exporters to control them. Ammonia, hydrogen sulphide and carbon dioxide, as well as wet and dry bulb temperature, dew point, air speed and depth of faeces that the sheep stood in, were measured on two ship voyages in which sheep were transported from Australia to the Middle East. Daily measurements were made at 20 measurement locations over 12 days. At four sites, the mean ammonia concentration for the voyage was above the recommended maximum limit for the live export industry (25 ppm). The mean ammonia concentrations at the remaining 16 sites were below 18 ppm and considered safe. High ammonia concentrations were localised and occurred particularly on closed decks, as well as at the front of the vessel and near the engine block on open decks. Ammonia concentration on the open decks was correlated with cumulative wind during the voyage, air speed, dew point, wet bulb temperature and faecal pad depth, and on the closed decks with dew point, and wet and dry bulb temperature. Hydrogen sulphide (<1.8 ppm) and carbon dioxide (<1900 ppm) concentrations were low and did not pose a risk to animal or human welfare or health. The results suggest that high ammonia concentrations occur in those parts of the ship where there is insufficient ventilation and/or high temperatures and humidity.

Oxalate nephropathy in a laboratory colony of common marmoset monkeys (Callithrix jacchus) following the ingestion of Eucalyptus viminalis.

Seven common marmoset monkeys (Callithrix jacchus) from a laboratory colony of 17 died over a period of eight months. Death of six of these monkeys was attributed to kidney failure from an oxalate-induced nephropathy. The epidemiology of this outbreak suggested an exogenous source and there was strong evidence that the source was bark and leaves from an Eucalyptus viminalis tree. Branches of this tree were introduced one month before the first death. The branches were removed one month after deaths commenced, but deaths continued for another five months. Urinalysis of all surviving marmosets at 80 and 122 days after initial contact with the E viminalis branches suggested that these monkeys had renal impairment. In the cases described here, the eating behaviour of common marmosets apparently exposed the animals to toxic levels of oxalate in the bark and leaves of an E viminalis tree.

Keloid histopathology after intralesional cryosurgery treatment.

BACKGROUND: Keloid presents a great healthcare challenge. The patients suffer from aesthetic disfiguration and occasionally from pruritus, pain and discomfort. Although various treatments are recommended, a single, highly effective treatment represents a great clinical need. OBJECTIVE: The cellular events and histopathology that follow intralesional cryosurgery were evaluated including cell proliferation, the number of cells expressing fibroblast markers, collagen synthesis and organization and mast cell infiltration. METHODS: Biopsies were collected before and after intralesional cryoneedle procedure. Collagen structure was evaluated with confocal microscopy. Mast cells, blood vessels and cell proliferation were evaluated using immunohistochemistry. RESULTS: Keloids contain abnormally thick collagen bundles, organized in swirls comprising closely bound fibrils. After intralesional cryosurgery, the collagen bundles lost their swirl structure, the thickness of the collagen layer decreased, and the bundles became more compact with less space between the fibres. A clear distinct transition zone separated the treated from the unaffected area. The frozen tissue was devoid of proliferating cells and mast cells whereas the number of blood vessels remained unaltered. Most of the fibroblasts expressed all tested myofibroblast markers although some exclusively expressed one and not the other. Few nuclei were observed in the affected area after treatment and very few of them expressed any fibroblast markers. CONCLUSIONS: Intralesional cryosurgery resulted in major changes in collagen structure and organization. The treatment reduced the number of proliferating cells, of myofibroblasts and of mast cells. These results may explain the reduction in no-response rate and the amelioration of the clinical symptoms after intralesional cryosurgery treatment.

The physiological and behavioral responses of steers to gaseous ammonia in simulated long-distance transport by ship.

Ammonia can accumulate in high-density cattle accommodation during live export shipments and potentially threaten the health and welfare of the animals. The effects of 4 NH(3) concentrations, control (<6), 11, 23, and 34 mg/m(3), on the physiology and behavior of steers were recorded. The animals were held for 12 d under a microclimate and stocking density similar to shipboard conditions experienced on voyages from Australia to the Middle East during the northern hemispheric summer. In bronchoalveolar lavage samples, ammonia increased (P < 0.05) macrophage activity in proportion to NH(3) concentration and increased (P < 0.05) neutrophil percentage at 23 and 34 mg/m(3), indicating active pulmonary inflammation. Ammonia also increased (P < 0.05) lacrimation, nasal secretions, and coughing, particularly at 34 mg/m(3), indicating that the NH(3) was irritating the mucous membranes of the eyes, nasal cavity, and respiratory tract. Ammonia had no effect (P > 0.05) on hematological variables or BW. Twenty-eight days after exposure to NH(3), the pulmonary macrophage activity and neutrophil concentrations of the steers had returned to normal. It was concluded that ammonia concentrations of 23 and 34 mg/m(3) induced temporary inflammatory responses, which indicate an adverse effect on the welfare of steers.

Osteopontin and calbindin gene expression in the eggshell gland as related to eggshell abnormalities.

Eggshell quality is a major concern to the poultry industry: eggs with poor-quality shells hatch poorly and are rejected in the processing plant. The eggshell gland (ESG) proteins and the matrix proteins, which participate in crystallization, fulfill important functions during formation of the calcified tissues and contribute to the biomechanical properties of the mature product. We selected layers that consistently produced eggshells with specific abnormalities, and continued to do so after molting, and evaluated the expression of 2 genes-osteopontin (OPN) and calbindin-as related to particular eggshell abnormalities. These genes are synthesized by the ESG and appear to participate in the calcification process. When the ESG produces normal eggshells, OPN was expressed uniformly by all of the epithelial cells facing the lumen, and calbindin was expressed by the glandular epithelium. In contrast, in the layers producing pimpled eggs, OPN was expressed only in sections of the pseudostratified epithelium, separated by areas of cells devoid of OPN gene expression, whereas calbindin was expressed at much greater levels throughout the glandular epithelium. Almost no OPN gene expression was observed in the ESG of layers producing corrugated shells, but their pattern of calbindin expression was similar to but somewhat greater than that in ESG that produced normal eggshells. In cases in which eggs had cracks at the sharp or blunt poles, OPN was expressed only at the side opposite to the cracks, whereas calbindin was expressed at both sides equally independent of the cracks. The results suggest that synthesis of the proteins associated with the formation of eggshells with the various abnormalities is controlled by different mechanisms. This may imply that more than 1 strategy will be required to improve eggshell quality.

Hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha), and heat-shock proteins in tibial dyschondroplasia.

Tibial dyschondroplasia (TD) is one of the most prevalent skeletal abnormalities in avian species; it causes economic losses and is an animal welfare problem. It has been hypothesized that the absence of vasculature in the lesion of the TD growth plates at the ends of the long bones is involved in the etiology of the disease. We evaluated the hypoxia status of normal and thiram-induced TD growth plates by immunostaining the protein adducts after pimonidazole hydrochloride administration. In addition, we evaluated the expression of hypoxia-inducible factor-1alpha (HIF-1alpha), the major regulator of the hypoxic response that is essential for chondrogenesis, and that of heat-shock proteins (Hsp) downstream from HIF-1alpha. We demonstrated that, in contrast to the normal growth plates, those afflicted by TD were hypoxic. A major increase in hypoxia was observed in the proliferative, hypertrophic, and calcified zones. In the normal growth plate, HIF-1alpha was expressed in chondrocytes of the articular cartilage and of the maturation zone, whereas in cases of TD, HIF-1alpha was also expressed in chondrocytes below the lesion. The expression level of HIF-1alpha was related to the severity of the disease, but was independent of its cause; the same pattern of expression was observed in growth plates of chicks selected for a high incidence of TD. No differentiation-dependent expression of HIF-1alpha was observed in response to hypoxia, as demonstrated by the use of primary cultures of growth plate chondrocytes. In the normal growth plates, Hsp90 and Hsp70 were localized to the maturation zone. More cells expressed both Hsp in the TD lesion. In conclusion, we demonstrated that the TD growth plate, in contrast to the normal one, is hypoxic, probably because of the lack of vascularization. Hypoxia leads to an increase in the transcription factor HIF-1alpha, causing increases in the levels of Hsp90 and Hsp70.

Damage maps for layered ceramics under simulated mastication.

Ceramic restorations, whether monolithic (single layer) or porcelain-veneered, often chip and fracture from repeated occlusal loading. Occlusion involves the opposing tooth sliding along the cuspal incline surface with an applied biting force (off-axis loading). We hypothesized that off-axis contact-load-slide-liftoff fatigue, as compared with normal axial fatigue loading, produces different fracture modes and fatigue lifespans of layered ceramics. Monolithic glass plates were epoxy-bonded to polycarbonate substrates as a transparent model for an all-ceramic crown on dentin. Off-axis and axial (control) cyclic loading was applied through a hard sphere in water, with a mouth-motion machine. The off-axis loading is more deleterious for contact-induced occlusal surface fracture, but less harmful for flexure-induced cementation surface fracture of brittle layers than the axial loading. This is because of the tangential load component associated with the off-axis loading. Clinical relevance is discussed.

Effect of temperature during the incubation period on tibial growth plate chondrocyte differentiation and the incidence of tibial dyschondroplasia.

Tibial dyschondroplasia (TD) is one of the most prevalent skeletal abnormalities in avian species, causing enormous economic losses and major animal welfare problems. Irregular cell differentiation of the chondrocytes that populate the growth plate has been hypothesized to be involved in the etiology of the disease. We evaluated the effect of incubation temperature at various stages of embryo development and bone formation on growth plate chondrocyte differentiation and the incidence of TD. Eggs were incubated either at a control temperature of 37.8 degrees C, or at 36.9 or 39 degrees C, each for 6 h/ d, during early (0 to 8 d) or late (10 to 18 d) embryo development. At 14 d of incubation and at hatch, tibias were collected and weighed, and their ash and calcium contents were determined. Growth plate chondrocyte differentiation was evaluated by alkaline phosphatase activity and collagen type II and osteopontin gene expression. In addition, the level of the heat-shock protein 90 (Hsp90) was evaluated by immunohistochemistry. The rest of the chicks were raised to 49 d and the incidence of TD was recorded. The incidence of TD increased only when the temperature was altered at the early stages of embryo development, and it was correlated with an increase in tibia ash but not with tibia weight or calcium content. Moreover, increased TD incidence was correlated with delayed chondrocyte differentiation. Early changes in incubation temperature caused an increase in the level of Hsp90 in articular and differentiated chondrocytes of the hypertrophic zone and in the numbers of distinct undifferentiated chondrocytes arranged in columns in the proliferative zone of the growth plate. In summary, the early stages of embryo development and bone formation are of utmost importantance for appropriate growth plate chondrocyte differentiation, and any temperature deviation will increase the subsequent incidence of TD. The increase in TD incidence is probably the result of delayed Hsp90-driven chondrocyte differentiation, supporting the hypothesis that TD is the result of abnormal chondrocyte differentiation.

Esposición accidental a energía láser en el medio laboral. Revisión de un caso clínico y de la literatura / Accidental exposition to lase energy in the work review of a clinical subject and the literature

Objetivo: Evaluar los riesgos de algunos trabajadores al estar expuestos a radiaciones de las cuales no conocen su longitud de onda. Método o literatura utilizada: Exposición de un caso clínico de exposicón a radiación electromagnética de longitud de onda no conocida en principio y revisión bibliográfica. Las bases de datos consultadas fueron MEDLINE, la legislación española de protección de trabajadores expuestos a radiaciones y la biblioteca del Centro de Especialidades Oftalmológicas de Madrid. Resultados: La exposición a láser de longitud de onda no conocida ha producido opacidedes de cristalino a un paciente joven. La legislación sobre riesgos laborales y la revisión de la literatura aporta suficiente documentación para evitar accidentes laborales y fomentar la prevención de riestos en el ámbito labora. Conclusiones: La exposición en el medio laboral a radiacciónes electromagnéticas puede ocasionar daños oculares y eventualemnte comprometer la visiónm. Todos los trabajadores en riesgo de exposición a radiación láser deberían usar los medios de protección ocular recomendados. En el caso de desconocer la longitud de onda del láser al que se está expuesto, se deben adoptar los niveles más rigurosos de protección (AU)

Objetive: To evaluate dangers for exposed workers form radiations of unknown wavelenght. Method or principle and literature: Exposition of a clinical subject to electromagnetic radition of unknown wavelenght and literature review Databases consulted ar ethe MEDLINE database, the Spanish labour legislation on exposicion to radiation and Library of the Speciality Centre Oftalmological from Madrid. Results: The exposition of unknown wavelenght Laser caused crystaline opacity. Legislation on labour dangers gets sufficient documentation to forbid accident and develop prevention in work environment. Conclusions: The exposition in work environment to electormagnetic radiation can provoke ocular injury and eventually compromise visio. Every workers in danger from exposition of Lase radiation should use recommanded ways to protect themself. In order to prevent unkown Laser wavelenght, most rigorous protection must be adopted (AU)

Fracture of porcelain-veneered structures in fatigue.

Porcelain-veneered crowns are widely used in modern dentistry, and their fracture remains problematic, especially in all-ceramic systems. We hypothesized that substructure properties have a significant effect on the longevity of porcelain-veneered crowns. Flat porcelain/metal or porcelain/ceramic structures were cemented to dentin-like composite, and a mouth-motion cyclic load of 200 N was delivered by means of a tungsten carbide spherical indenter (r = 3.18 mm), emulating occlusal loading on crowns supported by dentin. Findings indicated that porcelain on a low-hardness gold-infiltrated alloy was vulnerable to both occlusal surface contact damage and porcelain lower surface radial fracture, while porcelain on a higher-hardness palladium-silver alloy fractured chiefly from occlusal surface damage. The advantage of a high-modulus metal substructure was less pronounced. Fracture in the porcelain/zirconia system was limited to surface damage in the veneer layer, similar to that in the porcelain/palladium-silver system. Bulk fracture, observed in veneered alumina layers, was not found for zirconia.

Gene expression during chemically induced liver fibrosis: effect of halofuginone on TGF-beta signaling.

Hepatic fibrosis is associated with the activation of stellate cells (HSCs), the major source of extracellular matrix (ECM) proteins. Transforming growth factor-beta (TGF-beta), signaling via Smad3, is the most profibrogenic cytokine and the major promoter of ECM synthesis. Halofuginone, an inhibitor of liver fibrosis, inhibits TGF-beta-dependent Smad3 phosphorylation in human HSCs in culture. We have used transcriptional profiling to evaluate the effect of halofuginone on gene expression during the progression of thioacetamide (TAA)-induced liver fibrosis in the rat and have focused on genes that are associated with TGF-beta. TAA treatment causes alterations in the expression of 7% of liver genes. Halofuginone treatment prevents the changes in the expression of 41% of these genes and results in the inhibition of HSC activation and collagen synthesis. During the early stages of the disease, halofuginone affects genes involved in alcohol, lipid, protein, and phosphate metabolism and cell adhesion and, at later stages, in the cell cycle (cell development, differentiation, cell proliferation, and apoptosis). The activation of TGF-beta-dependent genes, such as tartrate-resistant acid phosphatase, its putative substrate osteopontin, stellate cell activation-association protein, and fibrillin-1, during chemically induced fibrosis is prevented by halofuginone. This study thus highlights the role of TGF-beta signaling in liver fibrosis and especially its potential for pharmacological intervention. Halofuginone, which has demonstrated efficacy and tolerance in animals and humans, could become an effective and novel therapy for liver fibrosis.

Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization.

The mechanical stimuli resulting from weight loading play an important role in mature bone remodeling. However, the effect of weight loading on the developmental process in young bones is less well understood. In this work, chicks were loaded with bags weighing 10% of their body weight during their rapid growth phase. The increased load reduced the length and diameter of the long bones. The average width of the bag-loaded group's growth plates was 75 +/- 4% that of the controls, and the plates showed increased mineralization. Northern blot analysis, in situ hybridization, and longitudinal cell counting of mechanically loaded growth plates showed narrowed expression zones of collagen types II and X compared with controls, with no differences between the relative proportions of those areas. An increase in osteopontin (OPN) expression with loading was most pronounced at the bone-cartilage interface. This extended expression overlapped with tartarate-resistant acid phosphatase staining and with the front of the mineralized matrix in the chondro-osseous junction. Moreover, weight loading enhanced the penetration of blood vessels into the growth plates and enhanced the gene expression of the matrix metalloproteinases MMP9 and MMP13 in those growth plates. On the basis of these results, we speculate that the mechanical strain on the chondrocytes in the growth plate causes overexpression of OPN, MMP9, and MMP13. The MMPs enable penetration of the blood vessels, which carry osteoclasts and osteoblasts. OPN recruits the osteoclasts to the cartilage-bone border, thus accelerating cartilage resorption in this zone and subsequent ossification which, in turn, contributes to the observed phenotype of narrower growth plate and shorter bones.

Suppression of hepatocellular carcinoma growth in mice by the alkaloid coccidiostat halofuginone.

Halofuginone, a widely used alkaloid coccidiostat, is a potent inhibitor of collagen alpha 1 (I) and matrix metalloproteinase 2 gene expression. Halofuginone also suppresses extracellular matrix deposition and fibroblast proliferation. It was recently shown to be effective in suppression of bladder carcinoma and glioma. This study sought to evaluate the effect of treatment with halofuginone on growth of hepatocellular carcinoma (HCC) in mice. Athymic Balb/c mice were injected subcutaneously with 10(7) human hepatoma cells (Hep3B), followed by treatment with halofuginone administered in the diet (750 microg/kg) starting on day 3, before tumour innoculation. The control group was received a normal diet. Mice were followed for survival, tumour volume and serum alpha-fetoprotein (alpha FP). The mechanism of the anti-tumour effect of halofuginone was determined in vitro by assessing tumour cell growth, and by measuring the serum concentrations of interferon-gamma (IFN gamma) and interleukin 2 (IL2). Halofuginone treatment induced almost complete tumour suppression in treated mice. Mortality rates were 10% and 50%, in halofuginone-treated and control mice, respectively (P<0.001). No visible tumour was observed in treated mice, as compared with a 364 mm3 tumour in control mice. Serum alpha FP were 0.1 and 212 ng/ml in treated and control mice, respectively (P<0.005). Halofuginone significantly inhibited HCC proliferation in vitro. Maximal inhibition of 64% of tumour cell growth was observed at a concentration of 10(-8) M. The anti-tumour effect was mediated via a significant increase in IFN gamma and IL2 (90 vs. 35, and 210 vs. 34 pg/ml in treated and control groups, respectively, P<0.005). Treatment with halofuginone effectively suppressed the progression of HCC in mice. This effect may be associated with a direct anti-tumour effect, and/or enhancement of a systemic immune response.

Saliva sampling to assess cortisol levels in unrestrained common marmosets and the effect of behavioral stress.

We report a method for taking saliva samples from unrestrained, captive marmosets (Callithrix jacchus) to assess levels of free cortisol. Saliva samples can be obtained reliably, without any habituation, by encouraging the marmosets to lick and chew a cotton-wool bud coated in banana. Saliva is thus left on the bud. We also tested sweetened fruit-drink crystals and a number of other substances, but none of these attracted all of the marmosets, and even flavors that were effective once soon lost their attraction. The presence of banana in the samples collected was found to lower the measured concentration of cortisol; however, as shown in samples taken with and without the banana coating on the bud, it did so in a linear and consistent way, and did not vary significantly among subjects. Therefore, a simple conversion factor could be applied to correct for the presence of banana. A first experiment showed that the marmosets exhibited a rise in salivary cortisol levels in response to social isolation. A second experiment showed elevation of cortisol during a period when the marmosets were disturbed by increased human activity and noise levels in the building in which they were housed. Hence, this method of saliva sampling is a convenient, noninvasive means of assessing cortisol levels in marmosets.