Impact of emergency access targets on admissions to general medicine: a retrospective cohort study.

BACKGROUND: Emergency access targets have been implemented Australia-wide following recent retrospective cohort studies linking emergency department (ED) overcrowding and excess mortality. AIM: To examine the impact of ED access targets on the characteristics and health service utilisation of general medicine (GM) inpatients at the Royal Melbourne Hospital. METHODS: A retrospective cohort study was conducted on all patient episodes admitted from ED to GM units from January 2009 to December 2012 (n = 15562), compared in two cohorts for 24 months before (n = 7393) and after (n = 8169) the implementation of the '4-h rule'. The main outcome measures were age, comorbidity, clinical urgency at presentation (Australasian Triage Score), ED and inpatient length of stay, diagnosis at discharge, and in-hospital complications. RESULTS: After the implementation of the '4-h rule', there was an increased proportion of younger patients aged ≤50 years (7.7-9.1%), urgent Australasian Triage Scale 3 (45.6-49.7%) and semi-urgent Australasian Triage Scale 4 (21.8-27.6%) patients admitted to GM. On average, GM patients had fewer comorbid conditions (proportion with Charlson score ≥6 decreased from 14.2% to 11.9%), and higher proportions (21.8-24.7%) were admitted for less than 48 h. CONCLUSION: Implementation of a 4-h access target has been associated with changes to the characteristics of patients admitted to GM, including higher proportions of younger patients, with fewer comorbid conditions and lower clinical urgency at presentation, although the latter may be explained by a coincidental change in the way that ED patients were triaged, as well as a greater number of these patients presenting to ED overall.

MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles.

Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood-brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.

Secretion of bicarbonate by rat distal tubules in vivo. Modulation by overnight fasting.

We have performed microperfusion studies on distal tubule bicarbonate reabsorption (JtCO2) of fed and fasted rats to extend our previous observations of in vivo bicarbonate secretion and to resolve certain discrepancies between free-flow and microperfusion data. When rats are fasted overnight, as in previous free-flow studies, distal tubule microperfusion with a 28-mM tCO2 solution results in significant JtCO2 (53 +/- 6 pmol.min-1.mm-1) at normal flow and increases briskly (91 +/- 16 pmol.min-1.mm-1) with bicarbonate load. This response is not influenced by the addition of other normal tubular fluid constituents. However, when normally fed rats are used, as in our previous microperfusion studies, distal tubule JtCO2 is not different from zero when a 28-mM tCO2 solution is perfused at normal flow rates but becomes negative (-54 +/- 13 pmol.min-1.mm-1) at high flow rates, which indicates the existence of bicarbonate secretion against a concentration gradient. Alkali loading of fasted rats also elicits bicarbonate secretion at high flow. These results demonstrate for the first time that normal feeding or alkali loading can induce bicarbonate secretion in a mammalian nephron segment in vivo, and resolves previous discrepancies between free-flow and microperfusion data.

Distal tubule bicarbonate accumulation in vivo. Effect of flow and transtubular bicarbonate gradients.

We have performed microperfusion studies on distal tubules of normal and alkalotic rats in an attempt to demonstrate in vivo bicarbonate secretion. All perfusion solutions were free of phosphate and other nonbicarbonate buffers. In both normal and alkalotic rats, distal perfusions elicited significant tCO2 entry only at high flow (24 nl/min). Even when perfusate tCO2 concentration closely matched plasma tCO2 concentration (30 mM tCO2), significant tCO2 entry again occurred at high flow. This was associated with a rise of the perfusate tCO2 concentration, which indicated net entry of tCO2 against a concentration gradient. In this "symmetrical" perfusion situation, acetazolamide blockade prevented tCO2 entry. Accordingly: distal tubule tCO2 entry is demonstrable in both alkalotic and normal rats at high flow rates; increasing perfusate tCO2 concentration can suppress tCO2 entry; and entry can occur in the absence of a gradient and this effect can be blocked by acetazolamide.

Proximal bicarbonate reabsorption during Ringer and albumin infusions in the rat.

Several studies have clearly shown that extracellular volume expansion is associated with suppression of whole kidney bicarbonate reabsorption, although little is known concerning the single nephron correlates of this response. More recently, attention has also been focussed on bicarbonate transport in attempts to identify a possible role for this ion in enhancing the rate of net fluid efflux by proximal tubules. To further explore proximal tubular bicarbonate handling in the rat, we carried out recollection micropuncture studies to assess the effects of infusions of modified Ringer or salt-poor hyperoncotic human albumin. With stable levels of arterial PCO2, plasma [HCO3-] or plasma [K+], marked suppression of fractional HCO3- reabsorption occurred: during Ringer infusion fractional reabsorption fell by 31% (P less than 0.001) while during albumin infusion a decrease of 20% (P less than 0.001) was observed. Despite this, absolute net HCO3- reabsorptive rates did not change significantly. Simple and partial correlation analysis of single tubular responses revealed strong linkage effects between changes in absolute net reabsorptive rates for HCO3- and H2O in both types of infusion; the partial r was 0.91 (P less than 0.001) and 0.94 (P less than 0.001) during Ringer and albumin infusions, respectively. We conclude that under these free-flow conditions, Ringer and albumin infusions do not suppress absolute net HCO3- reabsorption by proximal tubules, and that strongly linked changes in absolute HCO3- and H2O fluxes are characteristic of both protocols.

Comparison of black, green and rooibos tea on osteoblast activity.

Globally, tea is the second most consumed beverage after water. Habitual tea intake has been associated with higher bone mineral density, particularly in postmenopausal women. This association may be due to its polyphenols and resulting protective antioxidant effects. While in vivo studies have shown improved bone outcomes with a consumption of individual purified tea polyphenols, it is unclear if a particular tea - due to its different profiles of polyphenols - is more beneficial than others. Therefore, we compared three different types of commercially available teas on osteoblasts: green, black and rooibos tea. Tea was normalized to 1 or 10 µg per mL gallic acid equivalents to assess differences in outcomes based on tea profiles rather than the quantity of polyphenol naturally present. The lower level of polyphenols (1 µg per mL gallic acid equivalents) - regardless of tea type and thus polyphenol profile - resulted in greater mineral content as well as cellular and alkaline phosphatase activity in Saos2 cells. Moreover, this was associated with higher markers of differentiation (osteopontin, sclerostin) and reduced cellular toxicity and pro-inflammatory markers (IL6, TNFα). Green, black and rooibos tea improved osteoblast activity at the low level and support epidemiological evidence suggesting tea consumption may benefit bone heath.

Spinal Muscular Atrophy: More than a Disease of Motor Neurons?

Spinal muscular atrophy (SMA) is the most common genetically inherited neurodegenerative disease resulting in infant mortality. SMA is caused by genetic deletion or mutation in the survival of motor neuron 1 (SMN1) gene, which results in reduced levels of the survival of motor neuron (SMN) protein. SMN protein deficiency preferentially affects α- motor neurons, leading to their degeneration and subsequent atrophy of limb and trunk muscles, progressing to death in severe forms of the disease. More recent studies have shown that SMN protein depletion is detrimental to the functioning of other tissues including skeletal muscle, heart, autonomic and enteric nervous systems, metabolic/endocrine (e.g. pancreas), lymphatic, bone and reproductive system. In this review, we summarize studies discussing SMN protein's function in various cell and tissue types and their involvement in the context of SMA disease etiology. Taken together, these studies indicate that SMA is a multi-organ disease, which suggests that truly effective disease intervention may require body-wide correction of SMN protein levels.

Solvent stimulated actuation of polyurethane-based shape memory polymer foams using dimethyl sulfoxide and ethanol.

Solvent exposure has been investigated to trigger actuation of shape memory polymers (SMPs) as an alternative to direct heating. This study aimed to investigate the feasibility of using dimethyl sulfoxide (DMSO) and ethanol (EtOH) to stimulate polyurethane-based SMP foam actuation and the required solvent concentrations in water for rapid actuation of hydrophobic SMP foams. SMP foams exhibited decreased Tg when submerged in DMSO and EtOH when compared to water submersion. Kinetic DMA experiments showed minimal or no relaxation for all SMP foams in water within 30 min, while SMP foams submerged in EtOH exhibited rapid relaxation within 1 min of submersion. SMP foams expanded rapidly in high concentrations of DMSO and EtOH solutions, where complete recovery over 30 min was observed in DMSO concentrations greater than 90% and in EtOH concentrations greater than 20%. This study demonstrates that both DMSO and EtOH are effective at triggering volume recovery of polyurethane-based SMP foams, including in aqueous environments, and provides promise for use of this actuation technique in various applications.

Expression of the fusogenic p14 FAST protein from a replication-defective adenovirus vector does not provide a therapeutic benefit in an immunocompetent mouse model of cancer.

When injected directly into a tumor mass, adenovirus (Ad) vectors only transduce cells immediately along the injection tract. Expression of fusogenic proteins from the Ad vector can lead to syncytium formation, which efficiently spreads the therapeutic effect. Fusogenic proteins can also cause cancer cell death directly, and enhance the release of exosome-like particles containing tumor-associated antigens, which boosts the anti-tumor immune response. In this study, we have examined whether delivery of an early region 1 (E1)-deleted, replication-defective Ad vector encoding the reptilian reovirus p14 fusion-associated small transmembrane (FAST) protein can provide therapeutic efficacy in an immunocompetent mouse tumor model. A high multiplicity of infection of AdFAST is required to induce cell fusion in mouse mammary carcinoma 4T1 cells in vitro, and FAST protein expression caused a modest reduction in cell membrane integrity and metabolic activity compared with cells infected with a control vector. Cells expressing FAST protein released significantly higher quantities of exosomes. In immunocompetent Balb/C mice harboring subcutaneous 4T1 tumors, AdFAST did not induce detectable cancer cell fusion, promote tumor regression or prolong mouse survival compared with untreated mice. This study suggests that in the context of the 4T1 model, Ad-mediated FAST protein expression did not elicit a therapeutic effect.

Profiles, correlates, and trajectories of intelligence in Prader-Willi syndrome.

Three aspects of intellectual functioning in persons with Prader-Willi syndrome were examined in two, related studies. In study 1, 21 subjects were evaluated with a psychometric instrument that assesses neuropsychological styles of cognitive processing, the Kaufman Assessment Battery for Children. Prader-Willi subjects showed deficits in sequential processing, and strengths in academic achievement tasks such as reading and vocabulary. In contrast to previous reports on the syndrome, no relationship was found between weight and degree of intellectual impairment. Study 2 included a cross-sectional examination of the trajectory of IQ in 21 subjects aged 13 to 46 years, as well as a longitudinal analysis of 31 subjects aged 5 to 30 years who were tested twice with the same IQ test. No evidence of the previously described decline in IQ over time was noted in either the cross-sectional or longitudinal analyses. The implications of these findings for interventions are discussed.

Adaptive and maladaptive behavior in Prader-Willi syndrome.

The development and profiles of adaptive and maladaptive behavior of 21 adolescents and adults with Prader-Willi syndrome were cross-sectionally examined with the Vineland Adaptive Behavior Scales and Achenbach's Child Behavior Checklist (CBCL). Adaptive strengths emerged for the group as a whole in daily living skills, and this strength became more pronounced with increasing age. A relative weakness was found in socialization, most notably in coping skills. CBCL findings indicated that externalizing behaviors were particularly heightened in adolescence and that many behaviors previously described as either emerging or worsening in adolescence also persist into the adult years (e.g., temper tantrums, arguing, irritability, stubbornness, lying, skin picking, obsessions, defiance). Certain elevated CBCL behaviors were unique to young versus old age groups, and aging in this syndrome may be associated with heightened confusion, withdrawal, and fatigue. The need to study adaptive and maladaptive features in a wider age range of subjects with Prader-Willi syndrome was emphasized.

Models of helping and coping, responsibility attributions, and well-being in community elderly and their helpers.

The analysis of Brickman et al. (1982), which separates attribution of a problem's cause and solution, was tested in 4 studies. Young and elderly adults' (n = 210) well-being was related only to taking responsibility for solutions. The elderly compared with the young adults assumed less responsibility for problem cause and solution. They also preferred helping and coping models that assume low self-responsibility for solutions (e.g., medical model). This result was replicated with Meals on Wheels clients (n = 51). An intragenerational helping pattern was found in Study 3. Lay helpers (n = 63) helped mainly same-age recipients. Elderly and middle-aged helpers compared with young adults preferred using a medical model. Overall, a cohort bias in model preference was suggested. In Study 4, problem type and recipient age moderated attributions and model choice of young and middle-aged Ss (n = 92). Relevance to the control literature and ethical and clinical implications of a medical-model bias are discussed.

Functional categories and syntactic operations in (Ab)normal language acquisition.

This article argues in favor of the hypothesis that computational complexity determines order of acquisition of functional categories by normal children and patterns of impairment vs. relative preservation of these categories in children with Specific Language Impairment. Complexity is defined in terms of the properties of functional categories of the language the (ab)normal child is acquiring. The results of a study on present/past tense production and comprehension, carried out with children with and without Specific Language Impairment confirm the predictions of the computational complexity hypothesis. It is shown that it is easier to compute kernel functional categories than those that introduce further semantic modifications in the sentence.

Preliminary observations on the role of Acacia gum chemistry in Acacia utilization by Galago senegalensis in Kenya.

A census and preliminary observations on the ranging and feeding behavior of Galago senegalensis were made in a savannah-woodland site in Kenya. Population densities in three slightly different habitats were all approximately 1.5 animals/ha. Ranging patterns suggested the existence of territorial behavior. The diet of the galagos was exclusively insects and gums of two species of Acacia. The gum of A. drepanolobium appeared to be preferred to that of A. xanthophloea. The chemistry of the gums suggests that this preference is not due simply to the total level of phenolics or to avoidance of condensed tannins but may relate to the presence of compounds (e. g., flavonoids) having nutritional or hormonelike action.

Abnormal behaviors, with a special focus on rocking, and reproductive competence in a large sample of captive chimpanzees (Pan troglodytes).

Chimpanzees (Pan troglodytes) are endangered in the wild and may no longer be imported into the United States. Of those animals presently in captivity, candidates for breeding programs must be identified to insure a self-sustaining captive population. Some have suggested that poor reproductive performance might be linked to the performance of abnormal behaviors. In Study 1, three institutions housing breeding colonies of chimpanzees (86 males, 103 females) surveyed their animals for abnormal behaviors, copulatory performance, and, for females, maternal competence. In neither sex was there a positive association between absence of copulation and the presence of any of 18 forms of abnormal behavior. No one abnormal behavior was positively associated with inadequate maternal performance. Contrary to expectations, in both sexes (significantly for females), copulators exhibited more forms of abnormal behaviors than did noncopulators. In contrast, good mothers did show slightly fewer different forms of abnormal behaviors than did inadequate mothers. No specific combination of abnormal behaviors was associated with lack of copulatory performance in either sex or with inadequacy of maternal behavior. Significant sex differences occurred only in 2 of the 18 abnormal behaviors (coprophagy and self-clinging), both with females showing the higher prevalence. In Study 2, the rate of rocking in 5 male and 14 female chimpanzees at the Primate Foundation of Arizona was found to be relatively high among some reproductively competent subjects. Some rocking had forms and contexts indicative of aggressive displays. We conclude that chimpanzees should not be disregarded as potential breeders or as candidates for resocialization and breeding programs solely because they exhibit abnormal behaviors. Anyone involved in assessing well-being needs to be aware of individual differences among animals in the stimuli that may elicit rocking behavior. If they are strangers, they may elicit display rocking which does not indicate a lack of well-being. © 1992 Wiley-Liss, Inc.

The delusion of infection with HIV.

OBJECTIVE: This article briefly describes the consultation-liaison service of the HIV/AIDS service of the Royal North Shore Hospital, and reviews three men who had the delusional belief of being infected with HIV. METHOD: Twenty-three consecutive referrals from the HIV/AIDS unit to consultation-liaison psychiatry were reviewed. Three of these patients persistently believed that they were infected with HIV despite low risk factors and negative blood tests. RESULTS: These three men had a major depression. Two of the three patients were offered treatment with psychotherapy and antidepressant medication. The third declined psychiatric follow-up. CONCLUSION: The presentation of a patient for HIV testing, with an atypical history, should raise the interviewer's concern that there may be an underlying mental illness, in particular a depressive disorder.