Electrostatic Debye layer formed at a plasma-liquid interface.

We construct an analytic model for the electrostatic Debye layer formed at a plasma-liquid interface by combining the Gouy-Chapman theory for the liquid with a simple parabolic band model for the plasma sheath. The model predicts a nonlinear scaling between the plasma current density and the solution ionic strength, and we confirmed this behavior with measurements using a liquid-anode plasma. Plots of the measured current density as a function of ionic strength collapse the data and curve fits yield a plasma electron density of ∼10^{19}m^{-3} and an electric field of ∼10^{4}V/m on the liquid side of the interface. Because our theory is based firmly on fundamental physics, we believe it can be widely applied to many emerging technologies involving the interaction of low-temperature, nonequilibrium plasma with aqueous media, including plasma medicine and various plasma chemical synthesis techniques.

Safety and pharmacokinetics of the anti-orthopoxvirus compound ST-246 following a single daily oral dose for 14 days in human volunteers.

ST-246 is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. To this end, a phase 2, double-blind, randomized, placebo-controlled, multicenter trial was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of ST-246 when administered as a single daily oral dose (400 mg or 600 mg) for 14 days in fed adult volunteers. ST-246 was safe and well tolerated, with no deaths or serious adverse events reported during the study. There was a low incidence of treatment-emergent adverse events (TEAEs), the most common of which were mild nausea and headache. There were no clinically significant results from laboratory assessments, vital sign measurements, physical examinations, or electrocardiograms. The PK and dose proportionality of ST-246 were determined. The PK analysis showed that steady state was achieved by day 5 for the ST-246 400-mg treatment group and by day 6 for the 600-mg group. The dose proportionality analysis showed that the 400- and 600-mg ratio of dose-normalized peak drug concentration in plasma (C(max)) and relative exposure for each dosing interval (AUC(τ)) ranged from 80% to 85%. However, the 90% confidence intervals did not include 1.0, so dose proportionality could not be concluded. Overall, ST-246 was shown to be safe, and the PK was predictable. These results support further testing of ST-246 in a multicenter pivotal clinical safety study for licensure application.

Pharmacokinetic comparison of a single oral dose of polymorph form i versus form V capsules of the antiorthopoxvirus compound ST-246 in human volunteers.

ST-246, a novel compound that inhibits egress of orthopoxvirus from mammalian cells, is being tested as a treatment for pathogenic orthopoxvirus infections in humans. This phase I, double-blind, randomized, crossover, exploratory study was conducted to compare the pharmacokinetics (PK) of a single daily 400-mg oral dose of ST-246 polymorph form I versus polymorph form V administered to fed, healthy human volunteers. Both forms appeared to be well tolerated, with no serious adverse events. The order of administration of the two forms had no effect on the results of the PK analyses. Form I and form V both exhibited comparable plasma concentration versus time profiles, but complete bioequivalence between the two forms was not found. Maximum drug concentration (C(max)) met the bioequivalence criteria, as the 90% confidence interval (CI) was 80.6 to 96.9%. However, the area under the concentration-time curve from time zero to time t (AUC(0-t)) and AUC(0-∞) did not meet the bioequivalence criteria (CIs of 67.8 to 91.0% and 73.9 to 104.7%, respectively). The extent of absorption of form I, as defined by AUC(0-∞), was 11.7% lower than that of form V. Since ST-246 form I is more thermostable than form V, form I was selected for further development and use in all future studies.

Safety and pharmacokinetics of the antiorthopoxvirus compound ST-246 following repeat oral dosing in healthy adult subjects.

ST-246, a novel compound that inhibits egress of orthopoxvirus from infected cells, is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. This phase I, double-blind, randomized, placebo-controlled, escalating multiple-dose study was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 administered as a single daily oral dose of 250, 400, or 800 mg for 21 days to nonfasting healthy human volunteers. ST-246 appeared to be well tolerated, with no serious adverse events (AEs). Headache, for which one subject in the 800-mg group discontinued the study, was the most commonly reported AE in all treatment groups. The multiple-dose pharmacokinetics of ST-246 was well characterized. The day 21 mean elimination half-lives were calculated at 18.8, 19.8, and 20.7 h for each of the 250-, 400-, and 800-mg/day dose groups, respectively. Steady state was reached by day 6 (within 3 to 5 half-lives), saturable absorption was observed at the 800-mg dose level, and the fraction of parent drug excreted in the urine was very low. Based on these results, administration of 400 mg/day ST-246 can be expected to provide plasma concentrations above the efficacious concentration demonstrated in nonhuman primate models in earlier studies.

CE-based detection of methicillin-resistant Staphylococcus aureus.

Rapid and sensitive detection of methicillin-resistant Staphylococcus aureus is crucial for effective treatment and control of clinical infections caused by this bacterium. The goal of this study is to develop a CE-based detection method for multiplexed identification of a femA sequence specific for S. aureus and a unique mecA sequence encoding methicillin resistance. Blood samples spiked with known concentrations of bacteria were used for testing. Crude cell lysates were prepared by treating the spiked blood samples with DNazol Direct reagent and used as the template for isothermal amplification of mecA and femA genes. The amplified gene products then underwent a cycling probe reaction (CPR)-based assay to generate a short fluorophore-labeled oligonucleotide for detection in a CZE-LIF system. The assay enables a gene-specific fluorophore-labeled DNA-RNA-DNA chimeric probe to hybridize with complementary target in the presence of RNase H enzyme. The RNase H enzyme specifically cleaves probe RNA residues of the duplex, releasing a fluorophore fragment for detection and the target for recycling and hybridization with another chimeric probe. Intact and cleaved probe fragments were separated and detected using a CZE-LIF system. The limit of detection for isothermal amplification and CPR-CZE-LIF was approximately 10(4) colony-forming units of bacteria/mL of blood. This method accurately detects methicillin-resistant S. aureus within 3 h.

Professional carers' experiences of providing a pediatric palliative care service in Ireland.

In this article the authors present findings on professional carers' experience of providing pediatric palliative care to children with life-limiting conditions. For this qualitative study, part of a national pediatric palliative care needs analysis, the authors engaged in 15 focus group interviews and drew on the responses of open-ended questions to give voice to the experiences of professional carers and to situate the humanity of their caring reality. This humanity is articulated through three themes: clarity of definition and complexity of engagement, seeking to deliver a palliative care service, and the emotional cost of providing palliative care. Further analysis of these themes points to a work-life experience of skilled and emotional engagement with children, and their parents, in complex processes of caregiving and decision making. Pediatric palliative care occurs in an environment where parents shoulder a large burden of the care and professionals find themselves working in underresourced services.

Sarcoidosis diagnosed in elderly subjects: retrospective study of 30 cases.

STUDY OBJECTIVE: This study investigated the clinical features and disease course of sarcoidosis diagnosed in patients > 70 years of age. METHODS: A retrospective analysis was made of cases treated at the University Hospital in Nantes, France, between 1986 and 2000. The diagnosis of sarcoidosis was confirmed histopathologically. Cases involving progressive cancer and active tuberculosis were excluded. RESULTS: Thirty white patients with sarcoidosis diagnosed after age 70 years (mean, 74 years) were included. An alteration of general health (asthenia and/or anorexia and/or weight loss) was frequent (53%) and characteristic of the systemic form of the disease. Dyspnea was a fairly common sign (23%). The intrathoracic form of sarcoidosis was most frequent (43.3%). Diagnosis was difficult and lengthy, and symptomatology was atypical. Accessory salivary gland biopsy was an important contributing factor to diagnosis (70.6% were positive). Oral corticosteroid therapy was often required (60.7%). The disease course was satisfactory overall (81.8% of cases), but only for 50% of patients in intrathoracic stage IV. CONCLUSIONS: The clinical presentation of sarcoidosis in elderly subjects is mainly characterized by an alteration of general health. Diagnosis is difficult and should include accessory salivary gland biopsy. Therapy frequently involves corticosteroids. Overall prognosis is similar to that for young subjects.

Public health nursing in Ireland: a critical overview.

The World Health Organization have stressed the importance of nurses and midwives as a "force for health" in society's efforts to tackle the public health challenges of our time. The public health challenges are both diverse and complex. Principally, they emanate from a social model of health that takes cognizance of our behavior, our environment, and the historical, political, and cultural structures that facilitate health or militate against it. This paper provides a critical overview of public health nursing in Ireland, toward situating both our contribution to public health and some of the challenges that lie ahead of us. Specifically, it looks at nonquantifiable practice, where, through the presentation of stories, the wealth of public health nursing work is demonstrated in the ordinary voices of public health nurses. The potential risk of ignoring and minimizing the contribution of public health nursing in future developments in primary care in Ireland is discussed. Finally, it is proposed that public health nurses need to get political.