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The equine parasite Theilera equi continues to curtail global equine commerce due primarily to its ability to persist indefinitely in the immunocompetent horse. Details regarding the parasite life cycle, pathogenesis and mechanism of persistence remain unclear. The recently discovered T. haneyi is also capable of persistence in the horse, creating a potential reservoir for additional infections. These two divergent parasites share a unique gene family that expresses surface merozoite antigens, or equi merozoite antigens (EMAs). The EMA family was maintained in number and size in both parasites despite a species divergence of over 30 million years ago. This family is unique amongst Theilerias in number, structure and biochemical properties. In silico analysis revealed no evidence of selection for diversity within this family, indicating a role in host adaptation and persistence rather than antigenic variation and immune escape. Biochemical analysis revealed the presence of a conserved domain, homologous to the hemolysin toxin found in cobra venom. This finding combined with data from protein interaction prediction models may indicate interaction with the structural components of the host erythrocyte and a role in merozoite entry or escape. Additional predicted protein interactions focus on disruption of the enzymatic functions of the host cell, potentially resulting in enhanced parasite survival., (Copyright © 2018 Elsevier B.V. All rights reserved.)

GARDASIL®9, a 9-valent vaccine against human papillomavirus (9vHPV), was developed to prevent diseases mediated by HPV types 6/11/16/18/31/33/45/52/58. During the development of the vaccine, three nonclinical safety studies were conducted to evaluate repeat-dose toxicity and prenatal and postnatal developmental toxicity in Sprague-Dawley rats. In all studies, the vaccine was administered via intramuscular injections of 0.5 mL (the human dose) divided equally into each quadriceps muscle. In the repeat-dose toxicity study, potential local and systemic toxic effects of the 9vHPV vaccine were evaluated after 4 doses given 21 days apart and after a 21-day recovery period. In the prenatal study, virgin females were dosed at 5 and 2 weeks prior to mating and on Gestation Day [GD] 6 (3 total doses). Potential postnatal developmental toxicity of the vaccine formulation was evaluated after 4 total doses (premating to lactation). There were no treatment-related unscheduled deaths in any studies. In the 3-month repeat-dose toxicity study, no adverse effects in male or female rats were observed. Anticipated systemic effects representing immunological responses and local inflammatory reactions at the injection sites were noted in the vaccine-treated groups, with a trend toward recovery by the end of the 21-day recovery period. In the prenatal developmental toxicity study, there was no evidence of toxicity in females given the vaccine. There were no effects on fertility or reproductive performance of the parental females and no evidence of developmental toxicity. In the postnatal study, there was no evidence of toxicity in vaccine-treated females and no evidence of developmental toxicity based on standard postnatal parameters, including behavioral testing and reproductive performance. The vaccine induced antibody responses in all studies and vaccine-specific antibodies were detected in offspring in the developmental toxicity studies. These results support the favorable safety profile of GARDASIL®9., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400-μg/kg BPA in corn oil throughout pregnancy. From postnatal days 1 to 9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC was parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400-μg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400-μg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

General practitioner consultation data were used to compare the reactogenicity in infants of a 5-in-1 acellular pertussis vaccine (DTaP(5)/Hib/IPV) introduced in the United Kingdom in 2004 to the 4-in-1 whole cell-pertussis vaccine (DTwP/Hib) that it replaced. For each vaccine the incidence in the week following vaccination was compared to other periods to obtain a relative incidence. A lower relative incidence of crying, fever and local reactions was seen with DTaP(5)/Hib/IPV than DTwP/Hib. Although there were no other significant differences between vaccines the relative incidence was significantly above one on the day of vaccination for convulsions following DTwP/Hib and for apnoea/collapse following DTaP(5)/Hib/IPV., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Introduction: A variation in bone response to fluoride (F(-)) exposure has been attributed to genetic factors. Increasing fluoride doses (0 ppm, 25 ppm, 50 ppm, 100 ppm) for three inbred mouse strains with different susceptibilities to developing dental enamel fluorosis (A/J, a "susceptible" strain; SWR/J, an "intermediate" strain; 129P3/J, a "resistant" strain) had different effects on their cortical and trabecular bone mechanical properties. In this paper, the structural and material properties of the bone were evaluated to explain the previously observed changes in mechanical properties., Materials and Methods: This study assessed the effect of increasing fluoride doses on the bone formation, microarchitecture, mineralization and microhardness of the A/J, SWR/J and 129P3/J mouse strains. Bone microarchitecture was quantified with microcomputed tomography and strut analysis. Bone formation was evaluated by static histomorphometry. Bone mineralization was quantified with backscattered electron (BSE) imaging and powder X-ray diffraction. Microhardness measurements were taken from the vertebral bodies (cortical and trabecular bones) and the cortex of the distal femur., Results: Fluoride treatment had no significant effect on bone microarchitecture for any of the strains. All three strains demonstrated a significant increase in osteoid formation at the largest fluoride dose. Vertebral body trabecular bone BSE imaging revealed significantly decreased mineralization heterogeneity in the SWR/J strain at 50 ppm and 100 ppm F(-). The trabecular and cortical bone mineralization profiles showed a non-significant shift towards higher mineralization with increasing F(-) dose in the three strains. Powder X-ray diffraction showed significantly smaller crystals for the 129P3/J strain, and increased crystal width with increasing F(-) dose for all strains. There was no effect of F(-) on trabecular and cortical bone microhardness., Conclusion: Fluoride treatment had no significant effect on bone microarchitecture in these three strains. The increased osteoid formation and decreased mineralization heterogeneity support the theory that F(-) delays mineralization of new bone. The increasing crystal width with increasing F(-) dose confirms earlier results and correlates with most of the decreased mechanical properties. An increase in bone F(-) may affect the mineral-organic interfacial bonding and/or bone matrix proteins, interfering with bone crystal growth inhibition on the crystallite faces as well as bonding between the mineral and organic interface. The smaller bone crystallites of the 129P3/J (resistant) strain may indicate a stronger organic/inorganic interface, reducing crystallite growth rate and increasing interfacial mechanical strength.

Fractography has not been fully developed as a useful technique in assessing failure mechanisms of bone. While fracture surfaces of osteonal bone have been explored, this may not apply to conventional mechanical testing of mouse bone. Thus, the focus of this work was to develop and evaluate the efficacy of a fractography protocol for use in supplementing the interpretation of failure mechanisms in mouse bone. Micro-computed tomography and three-point bending were performed on femora of two groups of 6-month-old mice (C57BL/6 and a mixed strain background of 129SV/C57BL6). SEM images of fracture surfaces were collected, and areas of "tension", "compression" and "transition" were identified. Percent areas of roughness were identified and estimated within areas of "tension" and "compression" and subsequently compared to surface roughness measurements generated from an optical profiler. Porosity parameters were determined on the tensile side. Linear regression analysis was performed to evaluate correlations between certain parameters. Results show that 129 mice exhibit significantly increased bone mineral density (BMD), number of "large" pores, failure strength, elastic modulus and energy to failure compared to B6 mice (p<0.001). Both 129 and B6 mice exhibit significantly (p<0.01) more percent areas of tension (49+/-1%, 42+/-2%; respectively) compared to compression (26+/-2%, 31+/-1%; respectively). In terms of "roughness", B6 mice exhibit significantly less "rough" areas (30+/-4%) compared to "smooth" areas (70+/-4%) on the tensile side only (p<0.001). Qualitatively, 129 mice demonstrate more evidence of bone toughening through fiber bridging and loosely connected fiber bundles. The number of large pores is positively correlated with failure strength (p=0.004), elastic modulus (p=0.002) and energy to failure (p=0.041). Percent area of tensile surfaces is positively correlated with failure strength (p<0.001), elastic modulus (p=0.016) and BMD (p=0.037). Percent area of rough compressive surfaces is positively correlated with energy to failure (p=0.039). Evaluation of fracture surfaces has helped to explain why 129 mice have increased mechanical properties compared to B6 mice, namely via toughening mechanisms on the compressive side of failure. Several correlations exist between fractography parameters and mechanical behavior, supporting the utility of fractography with skeletal mouse models.

Introduction: The influence of genetic background on bone architecture and mechanical properties is well established. Nevertheless, to date, only few animal studies explore an underlying genetic basis for extrinsic factors effect such as fluoride effect on bone metabolism., Materials and Methods: This study assessed the effect of increasing fluoride doses (0 ppm, 25 ppm, 50 ppm, 100 ppm) on the bone properties in 3 inbred mouse strains that demonstrate different susceptibilities to developing enamel fluorosis (A/J a "susceptible" strain, 129P3/J a "resistant" strain and SWR/J an "intermediate" strain). Fluoride concentrations were determined in femora and vertebral bodies. Bone mineral density was evaluating through DEXA. Finally, three-point bend testing of femora, compression testing of vertebral bodies and femoral neck-fracture testing were performed to evaluate mechanical properties., Results: Concordant with increasing fluoride dose were significant increases of fluoride concentration in femora and vertebral bodies from all 3 strains. Fluoride treatment had little effect on the bone mineral densities (BMD) in the 3 strains. Mechanical testing showed significant alterations in "bone quality" in the A/J strain, whereas moderate alterations in "bone quality" in the SWR/J strain and no effects in the 129P3/J strain were observed., Conclusion: The results suggest that genetic factors may contribute to the variation in bone response to fluoride exposure and that fluoride might affect bone properties without altering BMD.

Objective: The objective of this study was to retrospectively analyze the last 100 consecutive emergency appendectomies performed in the authors' institution, which is a community-based teaching hospital, and look at the accuracy of the CT scan in the diagnosis of acute appendicitis., Design: Retrospective clinical study., Setting: A 600-bed community-based teaching hospital., Methods: The last 100 consecutive emergency appendectomies, which were performed at New York Methodist Hospital in 2004, were retrospectively analyzed. The collected data included the demographics of the patients, relevant history, physical examination, laboratory and radiological tests, and pathology results. The statistical analyses were performed using the JMP version 3.2 software (SAS Institute Inc., Cary, North Carolina). An alpha value of 0.05 was used in all statistical analyses, and p values were considered as being statistically significant at or below the alpha value of 0.05., Results: There was no statistically significant correlation between the acute appendicitis and some of the typical presenting symptoms and signs of acute appendicitis (rebound tenderness, low-grade fever, elevated white blood cell count, and anorexia). The sensitivity, specificity, positive predictive value, and negative predictive value of the CT scan in this retrospective analysis were 96%, 75%, 98.5%, and 50%, respectively, with an overall efficiency of 95%. However, the sensitivity, specificity, positive predictive value, and negative predictive value of the CT scan increased after reevaluation of the false-positive, false-negative, and inconclusive CT results by an experienced radiologist in a blind fashion (97%, 100%, 100%, and 71%, respectively). The correlation between the CT scan and the pathology result was statistically significant when the CT result was positive or negative (p = 0.0001)., Conclusion: The CT scan is indicated when the clinical presentation is equivocal, and it will be helpful if the result is positive or interpreted as negative only by an experienced radiology attending.

Background: Despite advances in surgical technique and materials, abdominal fascial closure has remained a procedure that often reflects a surgeon's personal preference with a reliance on tradition and anecdotal experience. The value of a particular abdominal fascial closure technique may be measured by the incidence of early and late wound complications, and the best abdominal closure technique should be fast, easy, and cost-effective, while preventing both early and late complications. This study addresses the closure of the vertical midline laparotomy incision., Data Sources: A MEDLINE (National Library of Medicine, Bethesda, Maryland) search was performed. All articles related to abdominal fascia closure published from 1966 to 2003 were included in the review., Conclusions: Careful analysis of the current surgical literature, including 4 recently published meta-analyses, indicates that a consistent conclusion can be made regarding an optimal technique. That technique involves mass closure, incorporating all of the layers of the abdominal wall (except skin) as 1 structure, in a simple running technique, using #1 or #2 absorbable monofilament suture material with a suture length to wound length ratio of 4 to 1.

The purpose of this investigation was to assess the ability of the hippocampus to withstand a metabolic challenge following chronic stress. An N-methyl-d-aspartate receptor excitotoxin (ibotenic acid, IBO) was infused into the CA3 region of the hippocampus following a period of restraint for 6 h/day/21 days. Following the end of restraint when CA3 dendritic retraction persists (3 to 4 days), rats were infused with IBO (or vehicle) into the CA3 region of the hippocampus. Stressed male rats showed significantly more CA3 damage after IBO infusion relative to controls and the saline-infused side. Moreover, IBO-exacerbation of damage in males was not observed in the CA3 region 3 to 4 days after acute stress (6 h restraint), nor in the CA1 region after chronic stress. Females were also examined and chronic stress did not exacerbate IBO damage in the CA3 region. Overall, these results demonstrate that chronic stress compromises the ability of the hippocampus to withstand a metabolic challenge days after the chronic stress regimen has subsided in male rats. Whether the conditions surrounding CA3 dendritic retraction in females represents vulnerability is less clear and warrants further investigation.

PURPOSE: The modern American surgeon is immersed in an ever-deepening sea of printed and electronic information. Although publishers know how many books and journals they sell, and journals can quote their calculated impact factor, no information exists whatsoever about what surgeons read. Which surgical journals are "popular," and how does it compare with their impact factor (IF)? Our objective was to assess the sources of information and reading habits of American surgeons and to compare the "popularity" of journals with their IFs.A questionnaire was mailed to 1000 American surgeons, randomly selected from a list provided by the American College of Surgeons.A total of 418 surgeons responded, and 371 responses could be analyzed (37%). The leading sources of medical information were medical literature (93%), professional meetings (88%), and CME courses (69%). The average time per surgeon/month dedicated to medical literature was 14 hours (range, 1 to 120). Peer-reviewed journals were read by 95%, textbooks by 68%, and update series by 60% of the respondents. The three most popular surgical journals were Annals of Surgery (IF, 5.40), selected by 60%; Journal of the American College of Surgery (IF, 1.87), selected by 48%; and Archives of Surgery (IF, 2.53), selected by 36%. The most popular subspecialty journals were Cancer (IF, 3.66), selected by 31%; Critical Care Medicine (IF, 3.74), selected by 17%; and Gastroenterology (IF, 10.33), selected by 12%. The New England Journal of Medicine (IF, 28.66), selected by 67%, and the Journal of the American Medical Association (IF, 9.55), selected by 66%, were the most popular general medical journals, followed by Mayo Clinic Proceedings (IF, 1.98), selected by 16%. Among the "leaders" on the IF list for international, British medical and surgical journals were Lancet (IF, 11.79), selected by 5%, and British Journal of Surgery (IF, 2.38), selected by 0.5% of the respondents.Those American surgeons responding consider published literature as their chief source of information, especially peer-reviewed journals. Overall, they ignore non-United States publications and select the journals they read without considering its IF.

The major signal transduction pathway for neurotensin (NT) receptors is the G-protein-dependent stimulation of phospholipase C, leading to the mobilization of intracellular free Ca2+ ([Ca2+]i) and the stimulation of cyclic GMP. We investigated the functional actions of an analog of NT(8-13), N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1), and other NT related analogs by quantitative measurement of the cytosolic free Ca2+ concentration in HT-29 (human colonic adenocarcinoma) cells using the Ca(2+)-sensitive dye fura-2/AM and by effects on cyclic GMP levels in rat cerebellar slices. The NT receptor binding affinities for these analogs to HT-29 cell membranes and newborn (10-day-old) mouse brain membranes were also investigated. Data obtained from HT-29 cell and mouse brain membrane preparations showed saturable single high-affinity sites and binding densities (Bmax) of 130.2 and 87.5 fmol/mg protein, respectively. The respective KD values were 0.47 and 0.39 nM, and the Hill coefficients were 0.99 and 0.92. The low-affinity levocabastine-sensitive site was not present (K1 > 10,000) in either membrane preparation. Although the correlation of binding between HT-29 cell membranes and mouse brain membranes was quite significant (r = 0.92), some of the reference agents had lower binding affinities in the HT-29 cell membranes. The metabolically stable compound NT1 plus other NT analogs and related peptides [NT, NT(8-13), xenopsin, neuromedin N, NT(9-13), kinetensin and (D-Trp11)-NT] increased intracellular Ca2+ levels in HT-29 cells, indicating NT receptor agonist properties. The effect of NT1 in mobilizing [Ca2+]i blocked by SR 48692, a non-peptide NT antagonist. Receptor binding affinities of NT analogs to HT-29 cell membranes were positively correlated with potencies for mobilizing intracellular calcium in the same cells. In addition, NT1 increased cyclic GMP levels in rat cerebellar slices, confirming the latter findings of its NT agonist action. These results substantiate the in vitro NT agonist properties of the hexapeptide NT analog NT1.

Diagnosis Related Group (DRG) hospital payment has begun to squeeze hospitals financially and is likely to do so in the future. This study analyzed the relationship between the volume of urologic procedures by an individual urologist, hospital costs per patient, and outcome. We used a three-year DRG database of urology patients (N = 2,980) at an academic medical center to analyze these. Low-volume urologists (arbitrarily defined by us) had higher hospital costs per patient, financial losses versus profits under DRGs, and a poorer outcome when compared with high-volume urologists. Pearson correlation showed a positive relationship between cost per patient and physician volume for nonemergency patients (-0.129, p less than 0.0001) and emergency patients (-0.368, p less than 0.0001). This may have been explained (in part) by a greater severity of illness for patients of low-volume urologists. These findings suggest, however, that the volume of urologic procedures per urologist may be related to hospital resource consumption. The health care financing environment of the future should provide substantial interest in this finding for those involved in the consumption of urologic services.

This study of 2,549 urology patients examined resource consumption by route of admission into the hospital. Almost all urologic admissions were more expensive as emergencies. These more expensive emergency urologic admissions had higher diagnostic costs, a longer hospital length of stay, and a greater severity of illness than their less expensive non-emergency counterpart. The more expensive emergency admission had a high referral rate to urology from non-urologic clinical services. These findings suggest that efficiency might be improved in the emergency urologic patients by increasing the speed of diagnosis and admission of patients to the appropriate clinical service (urology).

The Diagnostic Related Group (DRG) hospital payment system may be inequitable for certain groups of Medicare patients. This study of 216 Medicare urology patients in the ten non-age stratified urology DRGs demonstrated that patients seventy years of age and older (70+) had higher resource consumption than patients under seventy years of age (70-). Findings were: (1) older patients (70+) had higher total hospital costs (+12,022 per patient) than younger patients (70-) (+9,872 per patient); (2) a longer hospital length of stay (14.2 days vs 11.6 days); (3) financial risk of +1,756 loss per (70+) patient vs +1,309 profit per (70-) patient (p less than 0.05); (4) more diagnoses and procedures per patient, and (5) a higher mortality (4.0% vs 3.3%). These findings suggest that the current DRG scheme may be inequitable vis-a-vis the older urology patient in non-age stratified DRGs, and thus could limit access and quality of care for these patients in the future.

A case of choriocarcinoma presenting with metastases to both kidneys is reported. The epidemiologic and pathologic aspects of gestational choriocarcinoma are briefly discussed. Prior reports of renal metastases with choriocarcinoma are reviewed, and the fairly typical clinical presentation for this entity is emphasized.

The federal Medicare Diagnosis Related Group payment mechanism is undergoing constant change. Significant interest has been generated at the health policy level regarding reimbursement for patients with complications and comorbidities. The purpose of this study was to analyze hospital resource consumption for patients in the seventeen urology non-complicating condition (CC) stratified Diagnostic Related Groups (DRGs), currently 45 percent of urology DRGs. We analyzed 185 Medicare patients in these non-CC stratified urology DRGs and found that patients with more CCs per patient had higher total hospital costs per patient, financial risk under DRGs, a greater percentage of outliers, and a higher mortality, than patients in these same DRGs with fewer CCs per patient. These findings suggest that the current DRG system is inequitable to some patients and certain hospitals vis-a-vis non-CC stratified urology DRGs. The Health Care Financing Administration has not significantly changed the complicating condition urology DRG classification, as of its recent May, 1988 legislation. Financial disincentives to treat these patients may affect both their access and quality of care in the future.