Does lucency equate to revision? A five-year retrospective review of Attune and Triathlon total knee arthroplasty.

PURPOSE: The Attune® total knee arthroplasty system was introduced in 2013 to address lingering issues of patient dissatisfaction. However, recent literature reports concerns of early tibial tray debonding. The aim of this study was to compare the incidence of radiolucent lines, survivorship and patient reported outcome-measures between the Attune® system and the well-established Triathlon® system. METHODS: This retrospective database review was conducted at a single institution in Cork, Ireland. All primary Attune® (N = 445) and Triathlon® (N = 285) systems implanted between 2015 and 2016 were reviewed. Radiolucent lines were assessed for those with a minimum two-year radiological follow-up (Attune® = 338; Triathlon® = 231). X-rays were taken post op, at 6 months, 2 years and 5 years. Radiolucent lines were documented using the Modern Knee Society Radiographic System. Five-year survival was assessed using Kaplan-Meier analysis with the Log Rank method to determine statistical significance. The Oxford Knee Score and EQ-5D-5L, were collected pre-op, at 6 months, 2 years and 5 years post-operatively and compared using the Kruskal-Wallis Test. RESULTS: The Attune® had a higher proportion of radiolucent lines at the tibial tray [87.1% (54/62) vs 61.4% (27/44); p = 0.001] and at the implant-cement interface [62.9% (39/62) vs 43.2% (19/44); p = 0.02]. Conversely, the Triathlon® had a higher proportion AT the femur [38.6% (17/44) vs 12.9% (8/62); p = 0.001] and at the cement-bone interface [56.8% (25/44) vs 37.1% (23/62); p = 0.02]. The overall frequency of radiolucent lines was similar in both the Attune® and Triathlon® groups [17.8%, (60/338) vs 17.7%, (41/231); p = 0.49]. There was no difference in revision-free survival analysis at 5 years (Attune® 97.8% vs Triathlon® 95.8%; p = 0.129). The Attune® performed better at 5 years in the Oxford Knee Score [Attune® = 42.6 (SD 5.2) vs Triathlon® = 41 (SD 6.4); p = 0.001] and in the EQ-5D [Attune® = 0.773 (SD 0.187) vs Triathlon® = 0.729 (SD 0.218); p = 0.013]. There was no difference at 5 years in the EQ-VAS [Attune® = 80.4 (SD 13.7) vs Triathlon® = 78.5 (SD 15.3); p = 0.25]. CONCLUSION: The Attune® system exhibited a higher incidence of  radiolucent lines at the tibial tray. However, this did not lead to decreased survivorship at medium term follow-up compared to the Triathlon®. Furthermore, improvements in patient reported outcomes modestly favoured the Attune® system. LEVEL OF EVIDENCE: III.

tsRNAsearch: a pipeline for the identification of tRNA and ncRNA fragments from small RNA-sequencing data.

MOTIVATION: tRNAs were originally considered uni-functional RNA molecules involved in the delivery of amino acids to growing peptide chains on the ribosome. More recently, the liberation of tRNA fragments from tRNAs via specific enzyme cleavage has been characterized. Detection of tRNA fragments in sequencing data is difficult due to tRNA sequence redundancy and the short length of both tRNAs and their fragments. RESULTS: Here, we introduce tsRNAsearch, a Nextflow pipeline for the identification of differentially abundant tRNA fragments and other non-coding RNAs from small RNA-sequencing data. tsRNAsearch is intended for use when comparing two groups of datasets, such as control and treatment groups. tsRNAsearch comparatively searches for tRNAs and ncRNAs with irregular read distribution profiles (a proxy for RNA cleavage) using a combined score made up of four novel methods and a differential expression analysis, and reports the top ranked results in simple PDF and TEXT files. In this study, we used publicly available small RNA-seq data to replicate the identification of tsRNAs from chronic hepatitis-infected liver tissue data. In addition, we applied tsRNAsearch to pancreatic ductal adenocarcinoma (PDAC) and matched healthy pancreatic tissue small RNA-sequencing data. Our results support the identification of miR135b from the original study as a potential biomarker of PDAC and identify other potentially stronger miRNA biomarkers of PDAC. AVAILABILITY AND IMPLEMENTATION: https://github.com/GiantSpaceRobot/tsRNAsearch. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Diagnostic and Prognostic Circulating MicroRNA in Acute Stroke: A Systematic and Bioinformatic Analysis of Current Evidence.

BACKGROUND AND PURPOSE: Stroke is the second leading cause of death and disability worldwide and its diagnosis, and assessment of prognosis, remains challenging. There is a need for improved diagnostic and prognostic biomarkers. MicroRNAs (miRNAs) play important roles in the post-transcriptional regulation of gene expression and their secretion and remarkable stability in biofluids highlights their potential as sensitive biomarkers in the diagnosis and prognosis of acute stroke. METHODS: We carried out a systematic review to assess current evidence supporting the potential of miRNAs to act as unique diagnostic and prognostic biomarkers in blood samples collected from patients suffering acute stroke within 24 hours of symptoms onset. RESULTS: We identified 22 studies eligible for inclusion with 33 dysregulated miRNAs having diagnostic potential in the acute phase of the disease. We identified miR-16, miR-126, and miR-335 as having the highest sensitivity as diagnostic and prognostic biomarkers in acute ischaemic stroke and present original bioinformatic and pathway enrichment analysis of putative miRNA-target interactions. CONCLUSIONS: miRNAs represent unique biomarkers which have a promising future in stroke diagnosis and prognosis. However, there is a need for more standardized and consistent methodology for the accurate interpretation and translation of miRNAs as novel specific and sensitive biomarkers into clinical practice.

The spleen as a sanctuary site for residual leukemic cells following ABT-199 monotherapy in ETP-ALL.

B-cell lymphoma 2 (BCL-2) has recently emerged as a therapeutic target for early T-cell progenitor acute lymphoblastic leukemia (ETP-ALL), a high-risk subtype of human T-cell ALL. The major clinical challenge with targeted therapeutics, such as the BCL-2 inhibitor ABT-199, is the development of acquired resistance. We assessed the in vivo response of luciferase-positive LOUCY cells to ABT-199 monotherapy and observed specific residual disease in the splenic microenvironment. Of note, these results were confirmed by using a primary ETP-ALL patient-derived xenograft. Splenomegaly has previously been associated with poor prognosis in diverse types of leukemia. However, the exact mechanism by which the splenic microenvironment alters responses to specific targeted therapies remains largely unexplored. We show that residual LOUCY cells isolated from the spleen microenvironment displayed reduced BCL-2 dependence, which was accompanied by decreased BCL-2 expression levels. Notably, this phenotype of reduced BCL-2 dependence could be recapitulated by using human splenic fibroblast coculture experiments and was confirmed in an in vitro chronic ABT-199 resistance model of LOUCY. Finally, single-cell RNA-sequencing was used to show that ABT-199 triggers transcriptional changes in T-cell differentiation genes in leukemic cells obtained from the spleen microenvironment. Of note, increased expression of CD1a and sCD3 was also observed in ABT199-resistant LOUCY clones, further reinforcing the idea that a more differentiated leukemic population might display decreased sensitivity toward BCL-2 inhibition. Overall, our data reveal the spleen as a site of residual disease for ABT-199 treatment in ETP-ALL and provide evidence for plasticity in T-cell differentiation as a mechanism of therapy resistance.

Polymorphic centromere locations in the pathogenic yeast Candida parapsilosis.

Centromeres pose an evolutionary paradox: strongly conserved in function but rapidly changing in sequence and structure. However, in the absence of damage, centromere locations are usually conserved within a species. We report here that isolates of the pathogenic yeast species Candida parapsilosis show within-species polymorphism for the location of centromeres on two of its eight chromosomes. Its old centromeres have an inverted-repeat (IR) structure, whereas its new centromeres have no obvious structural features but are located within 30 kb of the old site. Centromeres can therefore move naturally from one chromosomal site to another, apparently spontaneously and in the absence of any significant changes in DNA sequence. Our observations are consistent with a model in which all centromeres are genetically determined, such as by the presence of short or long IRs or by the ability to form cruciforms. We also find that centromeres have been hotspots for genomic rearrangements in the C. parapsilosis clade.

Circulating miR-330-3p in Late Pregnancy is Associated with Pregnancy Outcomes Among Lean Women with GDM.

Gestational Diabetes Mellitus (GDM) is characterised by insulin resistance accompanied by reduced beta-cell compensation to increased insulin demand, typically observed in the second and third trimester and associated with adverse pregnancy outcomes. There is a need for a biomarker that can accurately monitor status and predict outcome in GDM, reducing foetal-maternal morbidity and mortality risks. To this end, circulating microRNAs (miRNAs) present themselves as promising candidates, stably expressed in serum and known to play crucial roles in regulation of glucose metabolism. We analysed circulating miRNA profiles in a cohort of GDM patients (n = 31) and nondiabetic controls (n = 29) during the third trimester for miRNA associated with insulin-secretory defects and glucose homeostasis. We identified miR-330-3p as being significantly upregulated in lean women with GDM compared to nondiabetic controls. Furthermore, increased levels of miR-330-3p were associated with better response to treatment (diet vs. insulin), with lower levels associated with exogenous insulin requirement. We observed miR-330-3p to be significantly related to the percentage of caesarean deliveries, with miR-330-3p expression significantly higher in spontaneously delivered GDM patients. We report this strong novel association of circulating miR-330-3p with risk of primary caesarean delivery as a pregnancy outcome linked with poor maternal glycaemic control, strengthening the growing body of evidence for roles of diabetes-associated miRNAs in glucose homeostasis and adaptation to the complex changes related to pregnancy.

Identification of an Exceptionally Long Intron in the HAC1 Gene of Candida parapsilosis.

The unfolded protein response (UPR) in the endoplasmic reticulum (ER) is well conserved in eukaryotes from metazoa to yeast. The transcription factor HAC1 is a major regulator of the UPR in many eukaryotes. Deleting HAC1 in the yeast Candida parapsilosis rendered cells more sensitive to DTT, a known inducer of the UPR. The deletion strain was also sensitive to Congo red, calcofluor white, and the antifungal drug ketoconazole, indicating that HAC1 has a role in cell wall maintenance. Transcriptomic analysis revealed that treatment of the wild type with DTT resulted in the increased expression of 368 genes. Comparison with mutant cells treated with DTT reveals that expression of 137 of these genes requires HAC1 Enriched GO term analysis includes response to ER stress, cell wall biogenesis and glycosylation. Orthologs of many of these are associated with UPR in Saccharomyces cerevisiae and Candida albicans Unconventional splicing of an intron from HAC1 mRNA is required to produce a functional transcription factor. The spliced intron varies in length from 19 bases in C. albicans to 379 bases in Candida glabrata, but has not been previously identified in Candida parapsilosis and related species. We used RNA-seq data and in silico analysis to identify the HAC1 intron in 12 species in the CTG-Ser1 clade. We show that the intron has undergone major contractions and expansions in this clade, reaching up to 848 bases. Exposure to DTT induced splicing of the long intron in C. parapsilosisHAC1, inducing the UPR.IMPORTANCE The unfolded protein response (UPR) responds to the build-up of misfolded proteins in the endoplasmic reticulum. The UPR has wide-ranging functions from fungal pathogenesis to applications in biotechnology. The UPR is regulated through the splicing of an unconventional intron in the HAC1 gene. This intron has been described in many fungal species and is of variable length. Until now it was believed that some members of the CTG-Ser1 clade such as C. parapsilosis did not contain an intron in HAC1, suggesting that the UPR was regulated in a different manner. Here we demonstrate that HAC1 plays an important role in regulating the UPR in C. parapsilosis We also identified an unusually long intron (626 bp) in C. parapsilosisHAC1 Further analysis showed that HAC1 orthologs in several species in the CTG-Ser1 clade contain long introns.

Hermansky-Pudlak syndrome with a novel genetic variant in HPS1 and subsequent accelerated pulmonary fibrosis: significance for phenocopy diseases.

The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA), bleeding diatheses and, in selected individuals, early-onset accelerated pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young man who presented following a self-directed literature review prompted by severe bleeding complications following minor surgical and dental procedures in the context of OCA. HPS was clinically suspected, with subsequent genetic testing confirming biallelic mutations in the HPS1 gene. Of interest, this is the only described HPS type 1 patient with two different (compound heterozygote) splice site variants in HPS1 In addition to detailing a novel genetic result and outlining the progressive clinical course of disease in this case, we discuss the management of HPS, the prognostic value of subtype analysis and the technical difficulties relating to transplantation in the case of HPS-associated advanced pulmonary fibrosis. This case also illustrates the concept of lung phenocopy relationships and the potential for elucidating the pathogenesis of more common pulmonary disorders by studying genetic diseases that result in similar phenotypes. Furthermore, it re-emphasises the importance of the patient voice, particularly with regard to complex diagnoses and rare diseases.

TPP riboswitch-dependent regulation of an ancient thiamin transporter in Candida.

Riboswitches are non-coding RNA molecules that regulate gene expression by binding to specific ligands. They are primarily found in bacteria. However, one riboswitch type, the thiamin pyrophosphate (TPP) riboswitch, has also been described in some plants, marine protists and fungi. We find that riboswitches are widespread in the budding yeasts (Saccharomycotina), and they are most common in homologs of DUR31, originally described as a spermidine transporter. We show that DUR31 (an ortholog of N. crassa gene NCU01977) encodes a thiamin transporter in Candida species. Using an RFP/riboswitch expression system, we show that the functional elements of the riboswitch are contained within the native intron of DUR31 from Candida parapsilosis, and that the riboswitch regulates splicing in a thiamin-dependent manner when RFP is constitutively expressed. The DUR31 gene has been lost from Saccharomyces, and may have been displaced by an alternative thiamin transporter. TPP riboswitches are also present in other putative transporters in yeasts and filamentous fungi. However, they are rare in thiamin biosynthesis genes THI4 and THI5 in the Saccharomycotina, and have been lost from all genes in the sequenced species in the family Saccharomycetaceae, including S. cerevisiae.

Identification of fungi in shotgun metagenomics datasets.

Metagenomics uses nucleic acid sequencing to characterize species diversity in different niches such as environmental biomes or the human microbiome. Most studies have used 16S rRNA amplicon sequencing to identify bacteria. However, the decreasing cost of sequencing has resulted in a gradual shift away from amplicon analyses and towards shotgun metagenomic sequencing. Shotgun metagenomic data can be used to identify a wide range of species, but have rarely been applied to fungal identification. Here, we develop a sequence classification pipeline, FindFungi, and use it to identify fungal sequences in public metagenome datasets. We focus primarily on animal metagenomes, especially those from pig and mouse microbiomes. We identified fungi in 39 of 70 datasets comprising 71 fungal species. At least 11 pathogenic species with zoonotic potential were identified, including Candida tropicalis. We identified Pseudogymnoascus species from 13 Antarctic soil samples initially analyzed for the presence of bacteria capable of degrading diesel oil. We also show that Candida tropicalis and Candida loboi are likely the same species. In addition, we identify several examples where contaminating DNA was erroneously included in fungal genome assemblies.

Finding optimal geometries for noise barrier tops using scaled experiments.

Scaled acoustic laboratory experiments are used to develop a methodology for obtaining the acoustic characteristics of different barrier top designs and for identifying geometries that may have advantages over the traditional thin vertical screen. The idea is to use a short impulsive spherical sound pulse possessing a broad frequency spectrum. If the duration of the pulse is sufficiently short, the entire primary signal, which travels by the shortest direct route diffracting at the top of the barrier, arrives at the receiver much earlier than any secondary signals reflected from the surroundings. Secondary signals may therefore be ignored and only the information from the primary signal can be analyzed. When the typical frequency band of the sound pulse is about an order of magnitude higher than typical traffic noise spectra, then scaled acoustic modeling using the same scaling factor for lengths and distances is possible. The results of such experiments are reported here for barriers with six different geometries. Using spectral analysis, insertion losses as functions of frequency were calculated for different source-receiver positions and barrier tops. The results were then rescaled for full-size traffic barriers and, using a typical traffic noise spectrum, single number ratings of barrier performance were obtained.

Identification of Non-Coding RNAs in the Candida parapsilosis Species Group.

The Candida CTG clade is a monophyletic group of fungal species that translates CTG as serine, and includes the pathogens Candida albicans and Candida parapsilosis. Research has typically focused on identifying protein-coding genes in these species. Here, we use bioinformatic and experimental approaches to annotate known classes of non-coding RNAs in three CTG-clade species, Candida parapsilosis, Candida orthopsilosis and Lodderomyces elongisporus. We also update the annotation of ncRNAs in the C. albicans genome. The majority of ncRNAs identified were snoRNAs. Approximately 50% of snoRNAs (including most of the C/D box class) are encoded in introns. Most are within mono- and polycistronic transcripts with no protein coding potential. Five polycistronic clusters of snoRNAs are highly conserved in fungi. In polycistronic regions, splicing occurs via the classical pathway, as well as by nested and recursive splicing. We identified spliceosomal small nuclear RNAs, the telomerase RNA component, signal recognition particle, RNase P RNA component and the related RNase MRP RNA component in all three genomes. Stem loop IV of the U2 spliceosomal RNA and the associated binding proteins were lost from the ancestor of C. parapsilosis and C. orthopsilosis, following the divergence from L. elongisporus. The RNA component of the MRP is longer in C. parapsilosis, C. orthopsilosis and L. elongisporus than in S. cerevisiae, but is substantially shorter than in C. albicans.

Mutagenicity of N-ethyl-N-nitrosourea, N-methyl-N-nitrosourea, methyl methanesulfonate and ethyl methanesulfonate in the developing Syrian hamster fetus.

N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU) are well-known direct-acting transplacental mutagens and carcinogens. Methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) are also direct-acting but more stable compounds and form a different proportion of the various methyl and ethyl DNA adducts. The transplacental mutagenicity and carcinogenicity of MMS and EMS have not been well characterized. We tested the mutagenicity to the developing Syrian hamster by these compounds under identical conditions and with a range of dose. Mutant fetal cells were selected for diphtheria toxin resistance. All four compounds were significantly mutagenic. MNU was the most active and MMS the least active of the compounds. ENU and MNU demonstrated linear dose-response curves, whereas that for EMS seemed to be supralinear over the range 0.125-0.5 mmol/kg. At its highest dose, EMS was comparable to ENU in mutagenicity. In view of a recent accidental exposure of pregnant women and others to EMS, further studies of this compound in animal models may be warranted.

Urethane and N-nitrosodiethylamine are mutagenic for the Syrian hamster fetus.

Urethane and N-nitrosodiethylamine are soluble environmental carcinogens that initiate tumors transplacentally, but have a mixed history of effectiveness in mutagenesis assays in vitro or in vivo with adult rodents. To test for their transplacental mutagenicity, Syrian hamster fetuses at 12 days in gestation were exposed transplacentally to urethane or N-nitrosodiethylamine at 0.5 or 1.0 mM/kg. The fetal cells were isolated on day 13 of gestation and tested for diphtheria toxin resistance as a mutation marker. Both compounds were significantly mutagenic, at both doses, causing 6- to 20-fold increases in mutations compared with controls. Compared with N-nitrosodiethylamine, urethane was somewhat more effective as a mutagen with a more marked dose-response. These results are consistent with mutagenesis as part of the mechanism of transplacental carcinogenicity of urethane and N-nitrosodiethylamine.

HGPRT mutation induction by N-ethyl-N-nitrosourea as measured by 6-thioguanine resistance is higher in male than in female Syrian hamster fetuses.

BACKGROUND: The consequences of mutations in embryonic and fetal cells are serious and contribute to high prenatal sensitivity to mutagenic agents. An understanding of the factors that influence the yield of such mutations is important for management of adverse effects of perinatal exposures. Resistance to 6-thioguanine (6-TG) can be utilized to study mutational events at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus. HGPRT is X-linked and recessive. According to the Lyon hypothesis, male cells have only one X-chromosome and female cells randomly inactivate the second X-chromosome. This leads to the prediction that X-linked genes should be equally sensitive to the mutagenic effects of toxicants in male and female fetuses. METHODS: We tested this supposition by in utero exposure of Syrian hamster fetuses to N-ethyl-N-nitrosourea (ENU) at day 12 of gestation. ENU is a strong carcinogen and mutagen. HGPRT mutations were detected by selection with 6-TG. RESULTS: Surprisingly. the male cells had 4 to 5 times more 6-TG mutants than female cells, in two separate experiments (p<0.001). Ouabain resistance, reflecting a co-dominant autosomal locus, was used as a control, and we found that there was no significant difference between male and female cells (p=0.549). CONCLUSIONS: Possible reasons for the sex difference in mutations include escape of the second X-chromosome from inactivation in some of the female cells, or higher mutability in male cells. In any event, there is a gender difference in vulnerability to mutation of an X-linked gene that has previously not been appreciated, and that may be relevant to toxicological studies of such genes. HGPRT is frequently used to monitor mutagenic events in human fetuses.

The forensic nurse practitioner role (emergency nursing)--potential response to changing health needs in New Zealand.

There is little existing policy related to Forensic Evidence collection in the Emergency Department environment within New Zealand (NZ). A case study based on the Christchurch Hospital Emergency Department (ChCh ED) environment is presented, which outlines the need to develop a specialised nursing role, that of Forensic Nurse Practitioner (emergency care). The role of nursing input in the field of Forensic Medicine in NZ is essentially limited to the psychiatric focus. While roles such as those of the Forensic Psychiatric Nurse are relatively well established, there is an apparent absence of other 'forensic' functions, in particular those related to victims or perpetrators of crime. It is an accepted feature of emergency care that serious injuries and deaths do occur despite intervention. In addition, there are significant numbers of patients who present as a result of assault or in suspicious circumstances. Awareness of the importance of forensic evidence collection, appropriate storage and disposal of material is growing. Legal implications have significance for nurses, in particular with the movement towards Advanced Nursing Practice with its focus on increasing autonomy, accountability and independent practice. In order to achieve holistic healthcare and to provide appropriate and effective interventions, forensic emergency nursing skills need to be developed.

The mutagenic effects of 7,12-dimethylbenz[a]anthacene, 3-methylcholanthrene and benzo[a]pyrene to the developing Syrian hamster fetus measured by an in vivo/in vitro mutation assay.

The transplacental mutagenicity of three polycylic aromatic hydrocarbons, 7,12-dimethylbenz[a]anthacene (DMBA), 3-methylcholanthrene (MC) and benzo[a]pyrene (BP), was measured by an in vivo/in vitro mutation assay. Fetal sensitivity and dose-response characteristics with regard to transplacental mutagenesis by these compounds have never been quantified. In the current experiment, pregnant Syrian hamsters were exposed to these compounds at day 12 of gestation. Twenty-four hours later the fetuses were removed and their cells were allowed a 5-day expression time in culture. They were then seeded for colony formation and also for mutation selection by diphtheria toxin. DMBA at 0.2 mmol/kg (51.3 mg/kg) had an induced mutant frequency of 1.56 x 10(-4) mutants per surviving cell. This was 598 times the historical control. DMBA at 0.2 mmol/kg was 3.6 times more potent than the highly mutagenic positive control, ethylnitrosourea, at 1 mmol/kg. DMBA also caused a dose-dependent increase in cloning efficiency, which was highly correlated with mutation rate. BP and MC were less effective than DMBA, causing increased mutations that were 31.6 and 17.7 times the historical control, respectively, and for neither was there any correlation of mutation rate with cloning efficiency. The special effectiveness of DMBA as a transplacental mutagen may relate to its ability to cause increased cell division and fixation of DNA lesions as mutations.

A telephone advice line does not decrease the number of presentations to Christchurch Emergency Department, but does decrease the number of phone callers seeking advice.

AIM: To describe the effect of a pilot national telephone advice service (Healthline) on a public hospital emergency department. METHODS: We prospectively gathered information from the Christchurch Hospital Emergency Department (ED) computer- and non-computer-based information systems, for a six-month period during the operation of Healthline. We compared the data with five earlier periods when Healthline was not running. In addition, Healthline collected and analysed data from call log information. RESULTS: There was a small increase (1.1%) in ED attendance during the study period. Patients referred by Healthline had a similar triage distribution to the general ED population, but a lower admission rate (29% vs 47%). Telephone calls to the ED dropped dramatically during the study period. CONCLUSIONS: Healthline had little effect on overall ED census and appeared to refer patients with similar acuity to the general ED census. It decreased the workload for ED nursing staff charged with answering advice calls.

Effect of a rapid assessment clinic on the waiting time to be seen by a doctor and the time spent in the department, for patients presenting to an urban emergency department: a controlled prospective trial.

AIMS: To test the hypothesis that triaging certain emergency department (ED) patients through a rapid assessment clinic (RAC) improves the waiting times, and times in the department, for all patients presenting to the emergency department. METHODS: For ten weeks an additional nurse and doctor were rostered. On the odd weeks, these two staff ran a RAC and on even weeks, they did not, but simply joined the other medical and nursing staff, managing patients in the traditional way. Patients suitable for triage to the RAC were those for whom disposal was readily apparent, interventions required were quickly undertaken, and lengthy investigations or assessment were not required. After the ten-week period data from the five weeks of the RAC and the five weeks with no RAC, but the same staffing level, were analysed and compared. RESULTS: During the five weeks of the RAC clinic a total of 2263 patients attended the ED, and 361 of these were referred to the RAC clinic. During the five control weeks a total of 2204 patients attended the ED. There was no significant difference in the distribution across triage categories between the RAC and non-RAC periods. The waiting times to be seen by a doctor show no difference at Triage 2 and 3 and a difference of several minutes for Triage 4 and 5 categories. The times patients spent in the ED also show no difference for Triage 2 and 3 and about 20 to 25 minutes advantage for RAC-week patients in Triage categories 4 and 5. CONCLUSIONS: The rapid management of patients with problems which do not require prolonged assessment or decision making, is beneficial not only to those patients, but also to other patients sharing the same, limited resources.

Effects of glucose on cloning efficiency and mutagenesis of fetal rat cells.

In a previous study, treatment of rats with 10% glucose in the drinking water, as fetuses during gestation and for 1.5 months after delivery, significantly enhanced tumor incidence that resulted from N-methyl-N-nitrosourea (MNU, 20 mg/kg) given transplacentally on gestation day 21, with a 1.6-fold increase in overall tumor incidence. We investigated whether glucose would have an effect on MNU-induced mutation in fetal F-344 rat somatic cells as measured in an in vivo/in vitro assay. Rat fetuses were exposed transplacentally to MNU on gestation day 16 and to a 10% glucose solution from gestation day 7 to day 17. Cells were isolated on gestation day 17 for determination of cloning efficiency and for selection of 6-thioguanine (6-TG)-resistant HGPRT mutants. Cloning efficiency of the fetal cells exposed to MNU alone was 22.6+/-2.3% S.E., while that for cells from fetuses exposed to MNU+glucose was 27.5+/-1.6% S.E., which was a significant difference (P=0.018). This indicates an effect of glucose on cell proliferation and survival. MNU treatment significantly increased the mutation frequency of fetal cells from a spontaneous value of 0.4 x 10(-6) per viable cell to (8.8+/-1.8 S.E.,) x 10(-6) (P=0.0087). The coexposure to MNU and glucose yielded a mutant frequency per plate of 0.62+/-0.05 S.E., which was a 1.5-fold increase compared to MNU alone (0.43+/-0.11 S.E., P=0.075. In summary, the data indicate that glucose during pregnancy increases proliferation/survival of fetal cells and possibly also mutation rate.