Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

Effect of private insurance incentive policy reforms on trends in coronary revascularisation procedures in the private and public health sectors in Western Australia: A cohort study

Background: The Australian federal government introduced private health insurance incentive policy reforms in 2000 that increased the uptake of private health insurance in Australia. There is currently a lack of evidence on the effect of the policy reforms on access to cardiovascular interventions in public and private hospitals in Australia. The aim was to investigate whether the increased private health insurance uptake influenced trends in emergency and elective coronary artery revascularisation procedures (CARPs) for private and public patients. Methods: We included 34,423 incident CARPs from Western Australia during 1995-2008 in this study. Rates of emergency and elective CARPs were stratified for publicly and privately funded patients. The average annual percent change (AAPC) in trend was calculated before and after 2000 using joinpoint regression. Results: The rate of emergency CARPs, which were predominantly percutaneous coronary interventions (PCIs) with stenting, increased throughout the study period for both public and private patients (AAPC=12.9%, 95% CI=5.0,22.0 and 14.1%, 95% CI=9.8,18.6, respectively) with no significant difference in trends before and after policy implementation. The rate of elective PCIs with stenting from 2000 onwards remained relatively stable for public patients (AAPC=−6.0, 95% C= −16.9,6.4), but increased by 4.1% on average annually (95% CI=1.8,6.3) for private patients (Pdifference=0.04 between groups). This rate increase for private patients was only seen in people aged over 65 years and people residing in high socioeconomic areas.Conclusions: The private health insurance incentive policy reforms are a likely contributing factor in the shift in 2000 from public to privately-funded elective PCIs with stenting. These reforms as well as the increasing number of private hospitals may have been successful in increasing the availability of publicly-funded beds since 2000

Deleterious Effects of Intermittent Recombinant Parathyroid Hormone on Cartilage Formation in a Rabbit Microfracture Model: a Preliminary Study

Intermittent parathyroid hormone administration can enhance fracture healing in an animal model. Despite the success of exogenous parathyroid hormone on fracture healing and spine fusion, few studies have examined the role of parathyroid hormone on cartilage formation. We determined the effects of intermittent parathyroid hormone on cartilage formation in a rabbit microfracture model of cartilage regeneration. Twelve rabbits were divided into three equal groups: (1) microfracture alone, (2) microfracture + parathyroid hormone daily for 7 days, and (3) microfracture + parathyroid hormone for 28 days. Nonoperated contralateral knees were used as controls. The animals were sacrificed at 3 months and gross and histologic analysis was performed. The microfracture alone group demonstrated the most healing on gross and histologic analysis. Treatment with either 1 or 4 weeks of parathyroid hormone inhibited cartilage formation. Although discouraging from a cartilage repair point of view, this study suggests that the role parathyroid hormone administration has in clinical fracture healing must be examined carefully. Although parathyroid hormone is beneficial to promote healing in spine fusion and midshaft fractures, its deleterious effects on cartilage formation suggests that it may have adverse effects on the outcomes of periarticular fractures such as tibial plateau injuries that require cartilage healing for a successful clinical outcome

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio

Stressor- and Corticotropin releasing Factor-induced Reinstatement and Active Stress-related Behavioral Responses are Augmented Following Long-access Cocaine Self-administration by Rats

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness. Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA). Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light–dark box after a 14- to 17-day extinction/withdrawal period. Results LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light–dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats. Conclusions When examined after several weeks of extinction/ withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry

The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results: Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2-2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02-8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5-2.4; p<0.001). Conclusion: HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality. © 2013 Gingo et al

In vivo incorporation of fenfluramine and norfenfluramine into pigmented and nonpigmented hair of rats measured by HPLC-fluorescence detection

The incorporation profiles for fenfluramine (Fen) and its metabolite norfenfluramine (Norf) into black hair and white hair of Zucker rats and into white hair of Wistar rats after intraperitoneal (i.p.) administration of Fen or N-nitrosofenfluramine (N-Fen) were studied in great detail. The target compounds were determined by high-performance liquid chromatography with fluorescence detection using 4-(4,5-diphenyl-1 H-imidazol-2-yl)benzoyl chloride as a derivatization reagent. After repeated i.p. administration of Fen (5 mg/kg) for 4 days to Zucker rats, shaft and root samples of black and white hair were obtained 1 week after the first administration. It was surprising that Fen and Norf levels in root samples of white hair were much higher than those in shaft or root samples of black hair, strongly suggesting that unknown mechanisms other than the action of melanin take place in the white hair root. Time course profiles for Fen and Norf after administration of a single i.p. dose of Fen or N-Fen were constructed for Zucker and Wistar rats. The percent level of Fen or Norf in white hair was 15-50% of that in black hair at any interval within 600 min after a single administration of Fen in Zucker rats. Even with Wistar rats having only white hair, we could demonstrate the time courses for incorporation of Fen and Norf into white hair. Finally, time course profiles for Fen and Norf were also followed after a single i.p. administration of N-Fen; this experiment showed that the levels of Norf were much higher than those of Fen for both black and white hair samples of Zucker rats at any interval tested

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Overview of the VA Quality Enhancement Research Initiative (QUERI) and QUERI theme articles: QUERI Series

<p>Abstract</p> <p>Background</p> <p>Continuing challenges to timely adoption of evidence-based clinical practices in healthcare have generated intense interest in the development and application of new implementation methods and frameworks. These challenges led the United States (U.S.) Department of Veterans Affairs (VA) to create the Quality Enhancement Research Initiative (QUERI) in the late 1990s. QUERI's purpose was to harness VA's health services research expertise and resources in an ongoing system-wide effort to improve the performance of the VA healthcare system and, thus, quality of care for veterans. QUERI in turn created a systematic means of involving VA researchers both in enhancing VA healthcare quality, by implementing evidence-based practices, and in contributing to the continuing development of implementation science.</p> <p>The efforts of VA researchers to improve healthcare delivery practices through QUERI and related initiatives are documented in a growing body of literature. The scientific frameworks and methodological approaches developed and employed by QUERI are less well described. A QUERI Series of articles in <it>Implementation Science </it>will illustrate many of these QUERI tools. This <it>Overview </it>article introduces both QUERI and the Series.</p> <p>Methods</p> <p>The <it>Overview </it>briefly explains the purpose and context of the QUERI Program. It then describes the following: the key operational structure of QUERI Centers, guiding frameworks designed to enhance implementation and related research, QUERI's progress and promise to date, and the Series' general content. QUERI's frameworks include a core set of steps for diagnosing and closing quality gaps and, simultaneously, advancing implementation science. Throughout the paper, the envisioned involvement and activities of VA researchers within QUERI Centers also are highlighted. The Series is then described, illustrating the use of QUERI frameworks and other tools designed to respond to implementation challenges.</p> <p>Conclusion</p> <p>QUERI's simultaneous pursuit of improvement and research goals within a large healthcare system may be unique. However, descriptions of this still-evolving effort, including its conceptual frameworks, methodological approaches, and enabling processes, should have applicability to implementation researchers in a range of health care settings. Thus, the <it>Series </it>is offered as a resource for other implementation research programs and researchers pursuing common goals in improving care and developing the field of implementation science.</p

Evaluation of glyceraldehyde-3-phosphate, prolylpeptidyl isomerase A, and a set of stably expressed genes as reference mRNAs in urate crystal inflammation

ABSTRACT