Concordance between physiotherapists and physicians for care of patients with musculoskeletal disorders presenting to the emergency department.

BACKGROUND: Overcrowding in emergency departments (ED) is a major concern worldwide. To answer increasing health care demands, new models of care including advanced practice physiotherapists (APP) have been implemented in EDs. The purpose of this study was to assess diagnostic, treatment and discharge plan concordance between APPs and ED physicians for patients consulting to the ED for minor musculoskeletal disorders (MSKD). METHODS: Patients presenting to two EDs in Montréal (Canada) with a minor MSKD were recruited and independently assessed by an APP and ED physician. Both providers had to formulate diagnosis, treatment and discharge plans. Cohen's kappa (κ) and Prevalence and Bias Adjusted Kappas (PABAK) with associated 95%CI were calculated. Chi Square and t-tests were used to compare treatment, discharge plan modalities and patient satisfaction between providers. RESULTS: One hundred and thirteen participants were recruited, mean age was 50.3 ± 17.4 years old and 51.3% had an atraumatic MSKD. Diagnostic inter-rater agreement between providers was very good (κ = 0.81; 95% CI: 0.72-0.90). In terms of treatment plan, APPs referred significantly more participants to physiotherapy care than ED physicians (κ = 0.27; PABAK = 0.27; 95% CI: 0.07-0.45; p = 0.003). There was a moderate inter-rater agreement (κ = 0.46; PABAK = 0.64; 95% CI: 0.46-0.77) for discharge plans. High patient satisfaction was reported with no significant differences between providers (p = 0.57). CONCLUSION: There was significant agreement between APPs and ED physicians in terms of diagnosis and discharge plans, but more discrepancies regarding treatment plans. These results tend to support the integration of APPs in ED settings, but further prospective evaluation of the efficiency of these types of models is warranted.

Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.

Acute myeloid leukemias (AMLs) result from a series of genetic events occurring in a stem or progenitor hematopoietic cell that gives rise to their clonal expansion and an impaired capacity to differentiate. To circumvent the genetic heterogeneity of AML patient cohorts, we have developed a model system, driven by the MLL-AF9 (MA9) oncogene, to generate multiple human leukemias using progenitor cells from a single healthy donor. Through stepwise RNA-sequencing data generated using this model and AML patients, we have identified consistent changes associated with MA9-driven leukemogenesis and demonstrate that no recurrent secondary mutations are required. We identify 39 biomarkers whose high expression level is specific to this genetic subtype of AML and validate that many of these have diagnostic utility. We further examined one biomarker, the receptor tyrosine kinase (RTK) RET, and show through shRNA knockdowns that its expression is essential for in vivo and in vitro growth of MA9-AML. These results highlight the value of novel human models of AML derived from single donors using specific oncogenic fusions to understand their biology and to uncover potential therapeutic targets.

Reciprocal inhibition of Cd and Ca uptake in isolated head kidney cells of rainbow trout (Oncorhynchus mykiss).

Some environmental pollutants, including cadmium (Cd) and zinc (Zn), can act as endocrine disruptors in fish, either in vivo or through a direct action on steroidogenic cells, as has been demonstrated in vitro. We have previously characterized Cd uptake in head kidney (homologue of mammalian adrenal) cells of rainbow trout (Oncorhynchus mykiss) and have provided evidence for a Cd/Ca interaction. Here, we pursued our investigation of metal competition for uptake. Our results show that inorganic speciation conditions favour Cd uptake with optimal level of accumulation for Cd2+ compared to chlorocomplexes (CdCl(n)(2-n)). Calcium uptake was studied for the first time in the fish head kidney cells and Ca was found to be less efficiently accumulated compared to Cd. A specific saturable mechanism of transport was characterized for Ca uptake but voltage-gated or La-sensitive cationic channels are unlikely to contribute appreciably. A concentration-dependent reciprocal inhibition was observed between Ca and Cd, whereas, Zn proved to inhibit Cd uptake exclusively. Additive inhibitory effect on Cd uptake was obtained with co-exposure to Ca and Zn. We conclude that Cd, but not Zn, may decrease Ca availability to the head kidney tissue. Also, Zn may partially protect against Cd toxicity but Zn would not protect against Cd-induced perturbation of Ca homeostasis.

In the wake of Hurricane Isabel: a prospective study of postevent trauma and injury control strategies.

Preventing hurricane-related injuries (HRI) has historically centered on the pre-event and event phases of the disaster. To date, no study has focused on injuries occurring during the postevent phase. We examined HRI that occurred after Hurricane Isabel struck a U.S. urban city. HRI presenting 1 week prior to the hurricane were collected from emergency department electronic records. HRI that presented to our level 1 trauma center were prospectively collected for 1 week after the hurricane. Nine hundred seventy-eight patients with possible HRI were identified. Fifty-one patients with trauma directly attributed to the hurricane were used for analysis. The number of HRI occurring before, during, and after the hurricane were 7 (14%), 3 (6%), and 41 (80%), respectively. The majority of HRI (37%) occurred on posthurricane day 1. Head, chest, upper and lower extremities accounted for 9 (18%), 8 (16%), 13 (26%), and 14 (28%) of HRI. More than one third of HRI patients were admitted to the hospital, and 12 (24%) underwent an operation. The average hospital length of stay was 4.7 days. Of our trauma alerts, 75 per cent had an Injury Severity Score (ISS) >8, and 20 per cent had an ISS >15. Tree-related injuries (TRI) accounted for 59 per cent of HRI. Males, ages 50-60, had the highest incidence of injury (63%). Significant injuries occur in the wake of a hurricane. Optimization of disaster preparation must include prevention strategies targeted to the postevent recovery phase of disasters.

Highly coherent light at 13 nm generated by use of quasi-phase-matched high-harmonic generation.

By measuring the fringe visibility in a Young's double pinhole experiment, we demonstrate that quasi-phase-matched high-harmonic generation produces beams with very high spatial coherence at wavelengths around 13 nm. To our knowledge these are the highest spatial coherence values ever measured at such short wavelengths from any source without spatial filtering. This results in a practical, small-scale, coherent, extreme-ultraviolet source that is useful for applications in metrology, imaging, and microscopy.

The phagosome proteome: insight into phagosome functions.

Phagosomes are key organelles for the innate ability of macrophages to participate in tissue remodeling, clear apoptotic cells, and restrict the spread of intracellular pathogens. To understand the functions of phagosomes, we initiated the systematic identification of their proteins. Using a proteomic approach, we identified >140 proteins associated with latex bead-containing phagosomes. Among these were hydrolases, proton pump ATPase subunits, and proteins of the fusion machinery, validating our approach. A series of unexpected proteins not previously described along the endocytic/phagocytic pathways were also identified, including the apoptotic proteins galectin3, Alix, and TRAIL, the anti-apoptotic protein 14-3-3, the lipid raft-enriched flotillin-1, the anti-microbial molecule lactadherin, and the small GTPase rab14. In addition, 24 spots from which the peptide masses could not be matched to entries in any database potentially represent new phagosomal proteins. The elaboration of a two-dimensional gel database of >160 identified spots allowed us to analyze how phagosome composition is modulated during phagolysosome biogenesis. Remarkably, during this process, hydrolases are not delivered in bulk to phagosomes, but are instead acquired sequentially. The systematic characterization of phagosome proteins provided new insights into phagosome functions and the protein or groups of proteins involved in and regulating these functions.

Sealing of polyester prostheses with autologous fibrin glue and bone marrow.

The purpose of this study was to develop a sealing technique for polyester prosthetic grafts able to promote healing and reduce intimal hyperplasia. The porcine experimental model was aortoiliac bypass with a 6-mm diameter knitted polyester prosthetic graft implanted for 14 and 90 days. Animals were divided into three groups according to sealing technique as follows: pre-clotting with blood (group I, n = 12), sealing with autologous fibrin glue (group II, n = 14), and sealing with autologous fibrin glue and bone marrow cells (group III, n = 16). Feasibility and quality of sealing were evaluated by scanning electron microscopy prior to implantation and by assessment of blood loss. After removal, prostheses were cut into three segments comprising the proximal anastomosis, midsection, and distal anastomosis. Pieces were fixed, embedded in paraffin, and serially sectioned for histologic study. Histological study focused on the degree of stenosis and hyperplasia of the neointima of each prosthesis. The results of this short-term study indicate that sealing of polyester vascular prosthetic grafts with autologous fibrin glue and bone marrow cells is effective in reducing intimal hyperplasia. However further study will be needed to assess long-term healing.

Use of the latissimus dorsi muscle to restore elbow flexion in arthrogryposis.

The successful use of ipsilateral pedicle latissimus dorsi muscle to restore elbow flexion in a child with arthrogryposis multiplex congenita is described. In appropriately selected patients, use of the latissimus dorsi muscle for elbow flexor reconstruction is a strong, reliable flexorplasty without significant donor-site morbidity.

Cloning and functional characterization of a cation-Cl- cotransporter-interacting protein.

To date, the cation-Cl(-) cotransporter (CCC) family comprises two branches of homologous membrane proteins. One branch includes the Na(+)-K(+)-Cl(-) cotransporters (NKCCs) and the Na(+)-Cl(-) cotransporter, and the other branch includes the K(+)-Cl(-) cotransporters. Here, we have isolated the first member of a third CCC family branch. This member shares approximately 25% identity in amino acid sequence with each of the other known mammalian CCCs. The corresponding cDNA, obtained from a human heart library and initially termed WO(3.3), encodes a 914-residue polypeptide of 96.2 kDa (calculated mass). Sequence analyses predict a 12-transmembrane domain (tm) region, two N-linked glycosylation sites between tm(5) and tm(6), and a large intracellular carboxyl terminus containing protein kinase C phosphorylation sites. Northern blot analysis uncovers an approximately 3.7-kilobase pair transcript present in muscle, placenta, brain, and kidney. With regard to function, WO(3. 3) expressed either in HEK-293 cells or Xenopus laevis oocytes does not increase Rb(+)-, Na(+)-, and Cl(-)-coupled transport during 5- or 6-h fluxes, respectively. In the oocyte, however, WO(3.3) specifically inhibits human NKCC1-mediated (86)Rb(+) flux. In addition, coimmunoprecipitation studies using lysates from WO(3. 3)-transfected HEK-293 cells suggest a direct interaction of WO(3.3) with endogenous NKCC. Thus, we have cloned and characterized the first putative heterologous CCC-interacting protein (CIP) known at present. CIP1 may be part of a novel family of proteins that modifies the activity or kinetics of CCCs through heterodimer formation.

Inhibition of Na(+)-K(+)-2Cl(-) cotransport by mercury.

Mercury alters the function of proteins by reacting with cysteinyl sulfhydryl (SH(-)) groups. The inorganic form (Hg(2+)) is toxic to epithelial tissues and interacts with various transport proteins including the Na(+) pump and Cl(-) channels. In this study, we determined whether the Na(+)-K(+)-Cl(-) cotransporter type 1 (NKCC1), a major ion pathway in secretory tissues, is also affected by mercurial substrates. To characterize the interaction, we measured the effect of Hg(2+) on ion transport by the secretory shark and human cotransporters expressed in HEK-293 cells. Our studies show that Hg(2+) inhibits Na(+)-K(+)-Cl(-) cotransport, with inhibitor constant (K(i)) values of 25 microM for the shark carrier (sNKCC1) and 43 microM for the human carrier. In further studies, we took advantage of species differences in Hg(2+) affinity to identify residues involved in the interaction. An analysis of human-shark chimeras and of an sNKCC1 mutant (Cys-697-->Leu) reveals that transmembrane domain 11 plays an essential role in Hg(2+) binding. We also show that modification of additional SH(-) groups by thiol-reacting compounds brings about inhibition and that the binding sites are not exposed on the extracellular face of the membrane.

Decreased amounts of antibodies to 22 and 18 kDa antigens in the peritoneal fluid of patients with endometriosis. LE Group d'Investigation en Gynecologie.

Accumulated evidence implicates immunological alterations in endometriosis. The purpose of this study was to look for variations in antibodies to distinct antigens in peritoneal fluid of women with and without endometriosis. Peritoneal fluid was aspirated from 17 women undergoing laparoscopy for tubal ligation and 37 patients complaining of symptoms of pain and /or infertility. Peritoneal fluid antibodies to a standard preparation of peritoneal fluid antigens were detected by Western blot analysis using peroxidase-labelled anti-human immunoglobulin G antibodies specific to the Fc region. Antibodies to distinct antigens were quantified by estimating the ratio of the relative optical density between samples and a standard amount of antibodies. Marked changes were found in the antibody detection to two antigens having apparent molecular weights of 22 and 18 kDa. The intensity of the antibody signal was significantly weaker in the peritoneal fluid from endometriosis patients (0.36 +/- 0.06 and 0.46 +/- 0.06) compared with that in women without endometriosis (0.62 +/- 0.08 and 0.75 +/- 0.06). It was also weaker in patients without endometriosis presenting with infertility (0.36 +/- 0.07 and 0.47 +/- 0.08), but only the 18 kDa antigen result was significant. After adjusting for infertility, the P values for the 18 and 22 kDa bands were 0.03 and 0.28 (not significant) respectively in the group of endometriosis patients. These changes were not related to the phase of the menstrual cycle. These data suggest an alteration in the immune response to two distinct antigens in the peritoneal fluid from women with endometriosis and infertility. Further evaluation of these two antigens and their antibodies would be of interest to help understand endometriosis and its associated infertility.

Decreased amounts of antibodies to 22 and 18 kDa antigens in the peritoneal fluid of patients with endometriosis

Accumulated evidence implicates immunological alterations in endometriosis. The purpose of this study was to look for variations in antibodies to distinct antigens in peritoneal fluid of women with and without endometriosis. Peritoneal fluid was aspirated from 17 women undergoing laparoscopy for tubal ligation and 37 patients complaining of symptoms of pain and/or infertility. Peritoneal fluid antibodies to a standard preparation of peritoneal fluid antigens were detected by Western blot analysis using peroxidase-labelled anti-human immunoglobulin G antibodies specific to the Fc region. Antibodies to distinct antigens were quantified by estimating the ratio of the relative optical density between samples and a standard amount of antibodies. Marked changes were found in the antibody detection to two antigens having apparent molecular weights of 22 and 18 kDa. The intensity of the antibody signal was significantly weaker in the peritoneal fluid from endometriosis patients (0.36 ± 0.06 and 0.46 ± 0.06) compared with that in women without endometriosis (0.62 ± 0.08 and 0.75 ± 0.06). It was also weaker in patients without endometriosis presenting with infertility (0.36 ± 0.07 and 0.47 ± 0.08), but only the 18 kDa antigen result was significant. After adjusting for infertility, the P values for the 18 and 22 kDa bands were 0.03 and 0.28 (not significant) respectively in the group of endometriosis patients. These changes were not related to the phase of the menstrual cycle. These data suggest an alteration in the immune response to two distinct antigens in the peritoneal fluid from women with endometriosis and infertility. Further evaluation of these two antigens and their antibodies would be of interest to help understand endometriosis and its associated infertility. Keywords: antibodies/antigens/endometriosis/peritoneal fluid/Western blot analysis

Identification and characterization of the G15D mutation found in a male patient with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency: alteration of the putative NAD-binding domain of type II 3 beta-HSD.

We report the detection of a homozygous G to A mutation converting codon Gly15 into Asp15 in the type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) gene in a male pseudo-hermaphrodite born from consanguineous parents and suffering from severe salt-losing 3 beta-HSD deficiency. To investigate further the potential involvement of residue 15 in the beta alpha beta dinucleotide-binding fold, we have studied the effect of substituting Gly15 for Ala15. We assessed the effect of the G15D and G15A missense mutations on enzymatic activity by analyzing mutant enzymes generated by site-directed mutagenesis of type II 3 beta-HSD cDNA after their transient expression in COS-1 cells. In intact transfected cells, after a 2-h incubation, the percentage of conversion of [3H]pregnenolone (PREG) into [3H]progesterone (PROG) was 35% and 50% for the G15A and native type II 3 beta-HSD enzymes, respectively, whereas no detectable activity was observed in cells expressing the G15D protein. This finding is in agreement with the severity of the disease in the homozygote G15D index case. On the other hand, in homogenates from cells transfected with the normal pCMV-type II 3 beta-HSD plasmid or with the mutated pCMV-G15D or pCMV-G15A plasmid, the Km values for PREG were 0.72 microM, 3.2 microM, and 3.4 microM, respectively, when incubated for 1 h in the presence of excess (1 mM) NAD+. Moreover, the expressed G15D and G15A proteins had decreased affinities for NAD+ with Km values of 113 microM and 148 microM, respectively, compared with 22 microM for normal type II 3 beta-HSD.(ABSTRACT TRUNCATED AT 250 WORDS)

Stratégies Cognitives et Processus D'autorégulation Chez Des Familles en Situation de Resolution de Problemes Logiques.

The family is a fundamental learning environment for many basic skills such as the ability to solve everyday domestic problems. A lack of competence in this type of problem solving would expose the individual to more frustration and possibly create the conditions for greater aggression. Forty-two low SES families, each including an aggressive boy, were invited to the laboratory for a problem-solving session on two occasions, at an interval of two years. Subjects were asked to find four preset combinations of colours by systematic permutations of four colours using a computer. Three types of cognitive performance were examined: resolution strategies, autoregulation strategies and the success rate in finding the solution. Results showed that most of the families were consistent in their use of anon-systematic strategy. Although some improvement in planning is observed during the second testing, no other improvement in autoregulation strategies was observed. In general, families had a better rate of success in finding the solution in the second session. The low cognitive level of these families and its stability are discussed.