Serological Responses of Raccoons and Striped Skunks to Ontario Rabies Vaccine Bait in West Virginia during 2012–2016

Since the 1990s, oral rabies vaccination (ORV) has been used successfully to halt the westward spread of the raccoon rabies virus (RV) variant from the eastern continental USA. Elimination of raccoon RV from the eastern USA has proven challenging across targeted raccoon (Procyon lotor) and striped skunk (Mephitis mephitis) populations impacted by raccoon RV. Field trial evaluations of the Ontario Rabies Vaccine Bait (ONRAB) were initiated to expand ORV products available to meet the rabies management goal of raccoon RV elimination. This study describes the continuation of a 2011 trial in West Virginia. Our objective was to evaluate raccoon and skunk response to ORV occurring in West Virginia for an additional two years (2012–2013) at 75 baits/km² followed by three years (2014–2016) of evaluation at 300 baits/km². We measured the change in rabies virus-neutralizing antibody (RVNA) seroprevalence in targeted wildlife populations by comparing levels pre- and post-ORV during each year of study. The increase in bait density from 75/km² to 300/km² corresponded to an increase in average post-ORV seroprevalence for raccoon and skunk populations. Raccoon population RVNA levels increased from 53% (300/565, 95% CI: 50–57%) to 82.0% (596/727, 95% CI: 79–85%) during this study, and skunk population RVNA levels increased from 11% (8/72, 95% CI: 6–20%) to 39% (51/130, 95% CI: 31–48%). The RVNA seroprevalence pre-ORV demonstrated an increasing trend across study years for both bait densities and species, indicating that multiple years of ORV may be necessary to achieve and maintain RVNA seroprevalence in target wildlife populations for the control and elimination of raccoon RV in the eastern USA.     

Liver Fibrosis in HIV Patients Receiving a Modern cART: Which Factors Play a Role?

Liver-related death in human immunodeficiency virus (HIV)-infected individuals is about 10 times higher compared with the general population, and the prevalence of significant liver fibrosis in those with HIV approaches 15%. The present study aimed to assess risk factors for development of hepatic fibrosis in HIV patients receiving a modern combination anti-retroviral therapy (cART).This cross-sectional prospective study included 432 HIV patients, of which 68 (16%) patients were anti-hepatitis C virus (HCV) positive and 23 (5%) were HBsAg positive.Health trajectory including clinical characteristics and liver fibrosis stage assessed by transient elastography were collected at inclusion. Liver stiffness values >7.1 kPa were considered as significant fibrosis, while values >12.5 kPa were defined as severe fibrosis. Logistic regression and Cox regression uni- and multivariate analyses were performed to identify independent factors associated with liver fibrosis.Significant liver fibrosis was detected in 10% of HIV mono-infected, in 37% of HCV co-infected patients, and in 18% of hepatitis B virus co-infected patients. The presence of diabetes mellitus (odds ratio [OR] = 4.6) and FIB4 score (OR = 2.4) were independently associated with presence of significant fibrosis in the whole cohort. Similarly, diabetes mellitus (OR = 5.4), adiposity (OR = 4.6), and the FIB4 score (OR = 3.3) were independently associated with significant fibrosis in HIV mono-infected patients. Importantly, cumulative cART duration protected, whereas persistent HIV viral replication promoted the development of significant liver fibrosis along the duration of HIV infection.Our findings strongly indicate that besides known risk factors like metabolic disorders, HIV may also have a direct effect on fibrogenesis. Successful cART leading to complete suppression of HIV replication might protect from development of liver fibrosis.     

The Impact of IMRT and Proton Radiotherapy on Secondary Cancer Incidence

BACKGROUND AND PURPOSE: There is concern about the increase of radiation-induced malignancies with the application of modern radiation treatment techniques such as intensity-modulated radiotherapy (IMRT) and proton radiotherapy. Therefore, X-ray scatter and neutron radiation as well as the impact of the primary dose distribution on secondary cancer incidence are analyzed. MATERIAL AND METHODS: The organ equivalent dose (OED) concept with a linear-exponential and a plateau dose-response curve was applied to dose distributions of 30 patients who received radiation therapy of prostate cancer. Three-dimensional conformal radiotherapy was used in eleven patients, another eleven patients received IMRT with 6-MV photons, and eight patients were treated with spot-scanned protons. The treatment plans were recalculated with 15-MV and 18-MV photons. Secondary cancer risk was estimated based on the OED for the different treatment techniques. RESULTS: A modest increase of 15% radiation-induced cancer results from IMRT using low energies (6 MV), compared to conventional four-field planning with 15-MV photons (plateau dose-response: 1%). The probability to develop a secondary cancer increases with IMRT of higher energies by 20% and 60% for 15 MV and 18 MV, respectively (plateau dose-response: 2% and 30%). The use of spot-scanned protons can reduce secondary cancer incidence as much as 50% (independent of dose-response). CONCLUSION: By including the primary dose distribution into the analysis of radiation-induced cancer incidence, the resulting increase in risk for secondary cancer using modern treatment techniques such as IMRT is not as dramatic as expected from earlier studies. By using 6-MV photons, only a moderate risk increase is expected. Spot-scanned protons are the treatment of choice in regard to secondary cancer incidence.     

Incidence and Prognosis of Organ Failure in Severely Injured Children and Adult Patients

Abstract Background: Does there exist a difference in the outcome of severely injured children and severely injured healthy adults? Methods: The data of 1,566 severely injured patients, treated between May 1998 and December 2002 in our emergency department of the University Essen/Germany, were analyzed. Patients with an injury severity score (ISS) > 24 were included in the present study. Patients younger as 18 (17) years were located to the children group c. Patients aged 18 and up to the age of 54 were included in the adult group a. Results: Fifty-four children and 252 adults met the selection criteria. ISS and the Glasgow coma scale (GCS) before intubation were not statistically different in both groups. Seriously injured children stayed significantly shorter on the intensive care unit, required significantly less ventilator days. Furthermore, the incidence of single organ failure (SOF) and multiple organ failure (MOF) was significantly lower in the children group. Mortality in the children group (29.6%) was lower than that in the adult group (33.7%). There was no death due to MOF in the children group as compared to 2.4% (n = 6) in the adults. Conclusion: The incidence of SOF and MOF was significantly lower in the children group although there was no difference in ISS, GCS and injury patterns. The prognosis of severely injured children was found to be better than those of adults. Moreover, there was no death due to MOF in the children group.     

Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

Using complexity theory to build interventions that improve health care delivery in primary care

Previous observational research confirms abundant variation in primary care practice. While variation is sometimes viewed as problematic, its presence may also be highly informative in uncovering ways to enhance health care delivery when it represents unique adaptations to the values and needs of people within the practice and interactions with the local community and health care system. We describe a theoretical perspective for use in developing interventions to improve care that acknowledges the uniqueness of primary care practices and encourages flexibility in the form of intervention implementation, while maintaining fidelity to its essential functions.     

Effects of verapamil on the pharmacokinetics and metabolism of epirubicin

Summary Experimental data suggest that multidrug resistance in cancer may be overcome by using an increased dose of anticancer agent(s) in combination with a resistance-modifying agent (RMA). We studied the pharmacokinetics and metabolism of both epirubicin (EPI) and verapamil (VPL) to explore the possible pharmacokinetic interactions between these two drugs. Ten patients with advanced breast cancer were given EPI (40 mg/m² in a daily i.v. bolus for 3 consecutive days), and five of them also received VPL (4×120 mg/daily p.o. for 4 consecutive days). The data indicated a significant interaction between these two drugs that affected their metabolism. The areas under the concentration-time curves (AUC) obtained for epirubicin glucuronide, epirubicinol glucuronide, and both of the 7-deoxy-aglycones were higher in the EPI+VPL group as compared with the EPI group. The AUC, terminal half-life, mean residence time, volume of distribution at steady state, and plasma clearance of EPI alone as compared with EPI+VPL did not differ significantly. These results suggest either an induction of enzymes necessary for drug metabolism or an increase in the liver blood flow, resulting in an enhanced generation of metabolites with time or in an inhibition of excretion processes. Comparisons of the AUC values obtained for EPI and its metabolites after the first, second, and third injections of EPI revealed a cumulative effect for the metabolites that was more pronounced in the EPI+VPL group, being significant (P<0.05) for epirubicin glucuronide in both treatment groups and for epirubicinol glucuronide in the EPI+VPL group. Maximal concentrations of VPL and nor-VPL reached 705±473 and 308±122 ng/ml, respectively, with the steady-state concentrations being 265±42 ng/ml for VPL and 180±12 ng/ml for nor-VPL.This study was supported by the Erich und Gertrud Roggenbuck-Stiftung zur Förderung der Krebsforschung (Hamburg). The anthracycline metabolites were kindly provided by Dr. A. Suarato (Farmitalia, Milano, Italy); nor verapamil was provided by Dr. Traugott (Knoll, Ludwigshafen, Germany)