MiR203 mediates subversion of stem cell properties during mammary epithelial differentiation via repression of ΔNP63α and promotes mesenchymal-to-epithelial transition.

During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, is robustly expressed in MaSCs and is required for preservation of self-renewing capacity in diverse epithelial structures. However, the mechanism(s) underlying subversion of this activity during forfeiture of self-renewing capacity are poorly understood. MicroRNAs (miRNAs) govern critical cellular functions including stem cell maintenance, development, cell cycle regulation and differentiation by disrupting translation of target mRNAs. Data presented here indicate that expression of miR203, a miRNA that targets ΔNp63α and ΔNp63ß is activated during luminal epithelial differentiation and that this pattern is observed in the murine mammary hierarchy. In addition, we present evidence that the transcription factor Zeb1 represses miR203 expression, thus enhancing ΔNp63α protein levels. Furthermore, ectopic miR203 suppresses ΔNp63α expression, proliferation and colony formation. The anti-clonogenic effects mediated by miR203 require suppression of ΔNp63α. In addition, ectopic miR203 promotes mesenchymal-to-epithelial transition and disrupts activities associated with epithelial stem cells. These studies support a model in which induction of miR203 mediates forfeiture of self-renewing capacity via suppression of ΔNp63α and may also have anti-tumorigenic activity through its reduction of EMT and cancer stem cell populations.

The effect of co-impregnated acids on the performance of Zn-based broad spectrum respirator carbons.

Impregnated activated carbons (IACs) that are used in multi-gas respirator applications usually contain copper and/or zinc impregnants. Co-impregnating with properly selected acids can improve the distribution of the metallic impregnant on the carbon and improve the gas adsorption capacity of the IAC. In this work a comparative study of some common acids co-impregnated with a zinc nitrate (Zn(NO(3))(2)) precursor is performed. The IACs were heated in an inert atmosphere at temperatures which promoted the thermal decomposition of Zn(NO(3))(2) to zinc oxide (ZnO). The gas adsorption properties of the IACs were tested using ammonia (NH(3)), sulphur dioxide (SO(2)) and hydrogen cyanide (HCN) challenge gases. Powder X-ray diffraction (XRD) was used to identify the impregnant species present after heating and to study impregnant distribution. Gravimetric analysis was used to determine the impregnant loading, and help to identify the impregnant species after heating. The interactions between the co-impregnated acid and Zn(NO(3))(2) precursor during heating are discussed. The relationship between impregnant species and gas adsorption capacity is discussed.

The effect of heating temperature and nitric acid treatments on the performance of Cu- and Zn-based broad spectrum respirator carbons.

Impregnated activated carbons (IACs) that are used in broad spectrum gas mask applications have historically contained copper and/or zinc impregnants. The addition of an oxidizing agent, such as nitric acid (HNO(3)) can be useful in distributing the metallic impregnants uniformly on the activated carbon substrate. In this work, we study IACs prepared from copper nitrate (Cu(NO(3))(2)) and zinc nitrate (Zn(NO(3))(2)) precursors as a function of HNO(3) content present in the impregnating solution and as a function of heating temperature. The gas adsorption capacity of the IACs was determined by dynamic flow testing using sulfur dioxide (SO(2)), ammonia (NH(3)), hydrogen cyanide (HCN) and cyclohexane (C(6)H(12)) challenge gases under dry and humid conditions. The thermal decomposition and distribution of the impregnant on the activated carbon substrate is studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermal analysis techniques. Relationships between gas adsorption capacity, impregnant distribution and the species of surface impregnants are discussed.

Consent, confidentiality and curing sexually transmitted infection: an ethical trilemma.

When treating contacts of patients with sexually transmitted infections (STIs), health professionals may face conflicting ethical imperatives. We surveyed middle grade doctors in genitourinary (GU) medicine and asked how they would manage a hypothetical clinical scenario. This was analysed on the basis of principles of respect for autonomy and beneficence/non-maleficence to assess how they weigh up duties of informed consent (autonomy of patient), partner confidentiality (autonomy of partner) and the need to achieve a good medical outcome. Responses indicated that the strategies that they employ in practice - what they actually say to patients (and what they leave unsaid) - balance the conflicting requirements of these ethical principles in quite different ways, some of which appear ethically problematic.

Escape and survival of Corophium volutator and Ilyanassa obsoleta exposed to freshwater and chlorothalonil.

The behavioural response and survival of marine mud snails and mud shrimp exposed to freshwater and the fungicide chlorothalonil (tetrachloroisophthalonitrile) was investigated. Amphipods were less tolerant of lower salinity than snails, with 50 and 76% survival associated with 5 and 0% seawater in freshwater, respectively. However, 50% of snails displayed a defence mechanism by retracting within their shell when exposed to 70% freshwater. Both species displayed an avoidance to chlorothalonil spiked at >100 ng/g and/or >100 ng/mL in sediments and seawater, respectively. The avoidance response of amphipods was observed along with a reduced swimming ability and increased lipid content. Snails displayed a higher susceptibility to physical stress, with an increased number unable to twist from being on their shell to their foot, and with longer righting time. Behaviour was affected at chlorothalonil concentrations of 0.001-0.01 ng/g and/or ng/mL, with a variability that could be due to degradation by the microbial community. Ascertaining the latter observations requires state-of-the-art chemical analyses.

Futilitarianism: knowing how much is enough in end-of-life health care.

The concept of futility is frequently invoked by doctors as providing ethical justification for the unilateral witholding/withdrawal of treatment of marginal benefit. The term now appears in many institutional policies. Yet it provokes controversy in its application, often being characterized as an unwarranted infringement of patient autonomy. This paper explores the substance of assertions of futility and attempts to dissect out the issues commonly intertwined in appeals to the concept. An ethical analysis of its component parts is presented using a principle-based approach to derive appropriate duties of care applicable in specific scenarios. The usefulness of the concept of futility is challenged and an alternative model is offered to deal with the ethical dilemmas posed by the availability of treatments of marginal benefit.

Rehydration in palliative and terminal care: if not--why not?

Patients who are in the last few days of life are often too frail to take oral fluids and nutrition. This may be due entirely to the natural history of their disease, although the use of sedative drugs for symptom relief may contribute to a reduced level of consciousness and thus a reduced oral intake. Rehydration with intravenous (i.v.) fluids is the usual response in acute care settings, whereas the hospice movement has often argued against this approach. The issues are complex and involve not only physical, psychological and social concerns, but also ethical dilemmas. A review of the literature gives conflicting reports of the physical discomfort that may be attributed to dehydration in dying patients. There are many confounding variables, including the concomitant use of antisecretory drugs, mouth breathing and oral infection. It remains unproven whether i.v. fluids offer symptomatic relief in this situation. Hospice doctors are concerned that the use of i.v. fluids gives confusing messages to relatives about the role of medical intervention at this stage in a patient's illness. A drip may cause a physical barrier between a patient and their loved one at this important time. The use of other methods of fluid replacement are discussed. In the absence of definitive research in this area, the balance of the burdens and benefits of such treatment remains subjective. The prime goal of any treatment in terminal care should be the comfort of the patient. Decisions should be made on an individual basis, involving both patients and their carers wherever possible. Prolonging life in such circumstances is of secondary concern and i.v. fluids given in this context may be futile. The ethical dilemmas of withholding and withdrawing medical treatment in addition to those of conducting research in this area are discussed.