Human bone marrow-derived mesenchymal stem cells rescue neonatal CPAP-induced airway hyperreactivity.

Continuous positive airway pressure (CPAP) is a primary non-invasive mode of respiratory support for preterm infants. However, emerging evidence suggests CPAP could be an underlying contributor to the unintended pathophysiology of wheezing and associated airway hyperreactivity (AHR) in former preterm infants. The therapeutic benefits of mesenchymal stem cells (MSCs) have been demonstrated in a variety of animal models and several clinical trials are currently underway to assess their safety profiles in the setting of prematurity and bronchopulmonary dysplasia (BPD). In the present study, using a mouse model of neonatal CPAP, we investigated whether conditioned medium harvested from cultures of human bone-marrow derived mesenchymal stem cells (hMSC) could rescue the CPAP-induced AHR, based upon previous observations of their anti-AHR properties. Newborn mice (male and female) were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for the first 7 postnatal days. At postnatal day 21 (two weeks after CPAP ended), lungs were removed, precision-cut lung slices were sectioned and incubated for 48 h in vitro in conditioned medium collected from cultures of three different hMSC donors. As expected, CPAP resulted in AHR to methacholine compared to untreated control mice. hMSC conditioned medium from the cultures of all three donors completely reversed AHR. These data reveal potential therapeutic benefits of hMSC therapy, which may be capable of rescuing the long-term adverse effects of neonatal CPAP on human airway function.

Single and Double Beta-Decay Q Values among the Triplet

The atomic mass relations among the mass triplet ^{96}Zr, ^{96}Nb, and ^{96}Mo have been determined by means of high-precision mass measurements using the JYFLTRAP mass spectrometer at the IGISOL facility of the University of Jyväskylä. We report Q values for the ^{96}Zr single and double ß decays to ^{96}Nb and ^{96}Mo, as well as the Q value for the ^{96}Nb single ß decay to ^{96}Mo, which are Q_{ß}(^{96}Zr)=163.96(13), Q_{ßß}(^{96}Zr)=3356.097(86), and Q_{ß}(^{96}Nb)=3192.05(16) keV. Of special importance is the ^{96}Zr single ß-decay Q value, which has never been determined directly. The single ß decay, whose main branch is fourfold unique forbidden, is an alternative decay path to the ^{96}Zr ßß decay, and its observation can provide one of the most direct tests of the neutrinoless ßß-decay nuclear-matrix-element calculations, as these can be simultaneously performed for both decay paths with no further assumptions. The theoretical single ß-decay rate has been re-evaluated using a shell-model approach, which indicates a ^{96}Zr single ß-decay lifetime within reach of an experimental verification. The uniqueness of the decay also makes such an experiment interesting for an investigation into the origin of the quenching of the axial-vector coupling constant g_{A}.

Legal impediments to data linkage.

Large numbers of electronic health data collections have been accumulated by both government and non-government agencies and organisations. Such collections primarily assist with the management of health services and the provision of health care programs, with only a minority of these data collections also intended for research purposes. A number of constraints are placed on access to such data for the purposes of research, including data linkage. This article examines those factors arising from the intricacies of Australia's privacy legislation landscape which impede access to such collections. The relevant issues discussed include issues relating to the existence of multiple privacy and health privacy Acts, the recommendations made by the Australian Law Reform Commission in relation to the Privacy Act 1988 (Cth) and the constraints placed on the conduct of data-linkage research which arise from legislation that relates specifically to certain data collections.

An ethics core curriculum for Australasian medical Schools.

Teaching ethics incorporates teaching of knowledge as well as skills and attitudes. Each of these requires different teaching and assessment methods. A core curriculum of ethics knowledge must address both the foundations of ethics and specific ethical topics. Ethical skills teaching focuses on the development of ethical awareness, moral reasoning, communication and collaborative action skills. Attitudes that are important for medical students to develop include honesty, integrity and trustworthiness, empathy and compassion, respect, and responsibility, as well as critical self-appraisal and commitment to lifelong education.

Should medical students act as surrogate patients for each other?

Until recently, most clinical teachers and medical students have regarded using medical students as surrogate patients for peer teaching of physical examinations and clinical skills as practical and uncontroversial. Recent changes to medical curricula and changes in hospitalized patient populations have led to questions about the ethical acceptability of this practice. This paper explores the ethical issues inherent in the use of medical students as surrogate patients. It suggests that, ethically, there are parallels with two situations: when students conduct physical examinations on patients and when students participate as subjects in research. Drawing on accepted ethical practice in these two germane areas, the paper argues that there are both ethical strengths and weaknesses in the practice of using students as surrogate patients. Strategies to promote free and informed involvement of students as surrogate patients are suggested.

What makes a problem an ethical problem? An empirical perspective on the nature of ethical problems in general practice.

Whilst there has been considerable debate about the fit between moral theory and moral reasoning in everyday life, the way in which moral problems are defined has rarely been questioned. This paper presents a qualitative analysis of interviews conducted with 15 general practitioners (GPs) in South Australia to argue that the way in which the bioethics literature defines an ethical dilemma captures only some of the range of lay views about the nature of ethical problems. The bioethics literature has defined ethical dilemmas in terms of conflict and choice between values, beliefs and options for action. While some of the views of some of the GPs in this study about the nature of their ethical dilemmas certainly accorded with this definition, other explanations of the ethical nature of their problems revolved around the publicity associated with the issues they were discussing, concern about their relationships with patients, and anxiety about threats to their integrity and reputation. The variety of views about what makes a problem a moral problem indicates that the moral domain is perhaps wider and richer than mainstream bioethics would generally allow.

HIV type 1 tat gene heteroduplex mobility assay as a tool to establish epidemiologic relationships among HIV type 1-infected individuals.

Molecular biology techniques are increasingly used to study the molecular epidemiology of infectious diseases. Most of these methods are expensive and labor-intensive. The human immunodeficiency virus (HIV) has substantial genomic variation, such that HIVs from different individuals are genetically diverse, although mutation rates differ for distinct regions of the genome. Most studies of HIV linkage and molecular evolution have focused on env or gag regions. We show that heteroduplex mobility analysis of the first exon of the HIV tat gene provides a simple, rapid, inexpensive, and reliable discriminatory tool for the molecular differentiation of shared versus distinct HIV-1 quasispecies when epidemiologic relations need to be defined. tat, as a relatively conserved region, appears to be a better region than the more variable env region to establish HIV-1 epidemiological linkages.

Selection for neutralization resistance of the simian/human immunodeficiency virus SHIVSF33A variant in vivo by virtue of sequence changes in the extracellular envelope glycoprotein that modify N-linked glycosylation.

We previously reported on the in vivo adaptation of an infectious molecular simian/human immunodeficiency virus (SHIV) clone, SHIVSF33, into a pathogenic biologic viral variant, designated SHIVSF33A. In the present study, we show that SHIVSF33A is resistant to neutralization by human immunodeficiency virus (HIV) and SHIV antisera. Multiple amino acid substitutions accumulated over time throughout the env gene of SHIVSF33A; some of them coincided with the acquisition of the neutralization resistance of the virus. Of interest are changes that resulted in the removal, repositioning, and addition of potential glycosylation sites within the V1, V2, and V3 regions of envelope gp120. To determine whether potential glycosylation changes within these principal neutralization domains of HIV type 1 formed the basis for the resistance to serum neutralization of SHIVSF33A, mutant viruses were generated on the backbone of parental SHIVSF33 and tested for their neutralization sensitivity. The mutations generated did not alter the in vitro replication kinetics or cytopathicity of the mutant viruses in T-cell lines. However, the removal of a potential glycosylation site in the V1 domain or the creation of such a site in the V3 domain did allow the virus to escape serum neutralization antibodies that recognized parental SHIVSF33. The combination of the V1 and V3 mutations conferred an additive effect on neutralization resistance over that of the single mutations. Taken together, these data suggest that (i) SHIV variants with changes in the Env SU can be selected in vivo primarily by virtue of their ability to escape neutralizing antibody recognition and (ii) carbohydrates play an important role in conferring neutralization escape, possibly by altering the structure of envelope gp120 or by shielding principal neutralization sites.

Ethics, DRGs and medical record administrators.

Medical record administrators in the United States have documented a range of ethical problems which they have experienced as a result of the advent of DRGs. This paper considers the similarities and differences between the Australian and United States experience of DRGs, and the implications of these for Australian medical record administrators. Some ethical problems are described, and it is argued that these problems relate particularly to power imbalances between medical record administrators and other health professions.

Persistence of type 5 adenovirus DNA in cells transformed by temperature-sensitive mutant, H5ts125.

The characteristic of H5ts125, a temperature-sensitive DNA-minus mutant, to transform 3 to 8 times more rat embryo cells than wild-type 5 adenovirus was correlated with the persistence of an increased proportion of the viral genome in cells independently transformed at the nonpermissive (39.5 degrees) or semipermissive (36 degrees) temperature. Reassociation kinetics of the hybridization of 32P-labeled,HindIII restriction fragments of the viral genome and excess unlabeled, transformed cell DNA was used to measure the quantity of the viral genome in transformed cells. Three of four cell lines independently transformed and maintained at 36 degrees contained all regions of the viral genome; one line transformed at 39.5 degrees contained multiple copies representing all of the viral DNA; and one line contained a large proportion of the viral genome. The cell line transformed and maintained at 32 degrees contained a quantity of viral genome consistent with that usually found in cells transformed by wild-type 5 adenovirus.