Prospective multicentre observational study assessing the tolerance and perception of patients using the Liquick Base catheter with an Ergothan tip.

INTRODUCTION: Intermittent self-catheterisation has revolutionised the management of neurogenic bladder-sphincter dysfunctions. The Liquick Base catheter is characterised by a streamlined Ergothan tip. The purpose of this study is to assess the tolerance and perception of patients using this catheter. MATERIALS AND METHODS: A French prospective multicentre observational study was conducted on patients with neurogenic bladder-sphincter dysfunctions. Upon inclusion in the study, the doctor completed a questionnaire on the patient's pathology. After 3 and 6 months, the doctor checked for neurogenic developments or observations and looked for any complications relating to intermittent self-catheterisation. The patient completed a questionnaire to assess his or her perception of using the catheter. RESULTS: Out of 42 patients included in the study, two were excluded. Out of the 40 assessed patients (30 males, 10 females) with an average age of 50.1±14.9 years, there were no reported cases of false passage. Bleeding occurred at least once in 10 patients (25%) in the first three months and in three out of 20 patients (15%) between 3 and 6 months. Two (5%) patients sought medical attention in the first three months for complications related to the catheter and 4 patients sought medical attention (10%) between 3 and 6 months. After 3 months 90% of patients were still using the catheter and after 6 months 90% of patients were still using the catheter. CONCLUSION: The Liquick Base catheter is well tolerated. Patient perception is positive for all parameters being examined, leading to the continued use of the catheter in 90% of cases. LEVEL OF EVIDENCE: 2.

Synchrotron FTIR and Raman spectroscopy provide unique spectral fingerprints for Arabidopsis floral stem vascular tissues.

Cell walls are highly complex structures that are modified during plant growth and development. For example, the development of phloem and xylem vascular cells, which participate in the transport of sugars and water as well as providing support, can be influenced by cell-specific wall composition. Here, we used synchrotron radiation-based Fourier-transform infrared (SR-FTIR) and Raman spectroscopy to analyse the cell wall composition of floral stem vascular tissues of wild-type Arabidopsis and the double-mutant sweet11-1 sweet12-1, which has impaired sugar transport. The SR-FTIR spectra showed that in addition to modified xylem cell wall composition, phloem cell walls in the double-mutant line were characterized by modified hemicellulose composition. Combining Raman spectroscopy with a classification and regression tree (CART) method identified combinations of Raman shifts that could distinguish xylem vessels and fibers. In addition, the disruption of the SWEET11 and SWEET12 genes impacted on xylem wall composition in a cell-specific manner, with changes in hemicelluloses and cellulose observed at the xylem vessel interface. These results suggest that the facilitated transport of sugars by transporters that exist between vascular parenchyma cells and conducting cells is important in ensuring correct phloem and xylem cell wall composition.

Tonicity inversely modulates lipocalin-2 (Lcn2/24p3/NGAL) receptor (SLC22A17) and Lcn2 expression via Wnt/ß-catenin signaling in renal inner medullary collecting duct cells: implications for cell fate and bacterial infection.

BACKGROUND: We have previously evidenced apical expression of the 24p3/NGAL/lipocalin-2 receptor (Lcn2-R; SLC22A17) in inner medullary collecting duct (IMCD) cells, which are present in vivo in a hyperosmotic/-tonic environment that activates canonical Wnt/ß-catenin signaling. The localization of Lcn2-R in the inner medulla is intriguing considering local bacterial infections trigger toll-like receptor-4 (TLR-4)-mediated secretion of the bacteriostatic Fe3+-free (apo-)Lcn2. AIM: To determine the effects of osmolarity/tonicity changes, Wnt/ß-catenin and TLR-4 activation on Lcn2-R and Lcn2 expression and cell viability in rat primary IMCD and mouse (m)IMCD3 cells. METHODS: Normosmolarity/-tonicity was 300 mosmol/l whereas hyperosmolarity/-tonicity was induced by adding 100 mmol/l NaCl + 100 mmol/l urea (600 mosmol/l, 1-7 days). Lcn2-R and Lcn2 expression were determined by qPCR, immunoblotting, flow cytometry and immunofluorescence microscopy. ß-catenin was silenced by RNAi. Cell viability/death was determined with MTT and LDH release assays. TLR-4 was activated by bacterial lipopolysaccharides (LPS). RESULTS: Hyperosmotic/-tonic media upregulated Lcn2-R by ~4-fold and decreased Lcn2 expression/secretion, along with Wnt/ß-catenin activation, in IMCD cells. These effects of hyperosmotic/-tonic media on Lcn2-R/Lcn2 expression were reverted by normosmolarity/-tonicity, ß-catenin silencing and/or LPS. Exposure of cells with endogenous or stably overexpressing Lcn2-R to apo-Lcn2 or LPS decreased cell viability. CONCLUSIONS: Lcn2-R upregulation and Lcn2 downregulation via Wnt/ß-catenin may promote adaptive osmotolerant survival of IMCD cells in response to hyperosmolarity/-tonicity whereas Lcn2 upregulation and Lcn2-R downregulation via TLR-4 and/or normosmolarity/-tonicity may protect IMCD cells against bacterial infections and prevent autocrine death induction by Lcn2.

Diagnostic accuracy of the ADOS and ADOS-2 in clinical practice.

The Autism Diagnostic Observation Schedule is a semi-structured, standardized assessment tool for individuals with suspected autism spectrum disorders (ASD) and is deemed to be part of the gold standard for diagnostic evaluation. Good diagnostic accuracy and interpersonal objectivity have been demonstrated for the ADOS in research setting. The question arises whether this is also true for daily clinical practice and whether diagnostic accuracy depends on specialized experience in the diagnostic evaluation. The present study explores the diagnostic accuracy of the original and the revised version of the ADOS for Modules 1 through 4. Thus, seven cases of ADOS executions were recorded and coded by a group of experts of specialized outpatient clinics for ASD. In an extensive consensus process, including video analysis of every minute of the ADOS executions, a "gold standard" coding for every case was defined. The videos of the ADOS administration were presented to a large group of clinicians (from daily clinical routine care) and their codings (n = 189) were obtained and analysed. Variance of coding and congruence with the expert coding were determined. High variance was found in the codings. The accuracy of the coding depends on the experience of the coder with the ADOS as well as on characteristics of the cases and the quality of the administration of the ADOS. Specialization in the diagnostic of ASD has to be claimed. Specialized outpatient clinics for ASD are required which guarantee a qualified diagnostic/differential diagnostic and case management with the aim of demand-oriented supply of individual cases.

Effects of multisensory integration processes on response inhibition in adolescent autism spectrum disorder.

BACKGROUND: In everyday life it is often required to integrate multisensory input to successfully conduct response inhibition (RI) and thus major executive control processes. Both RI and multisensory processes have been suggested to be altered in autism spectrum disorder (ASD). It is, however, unclear which neurophysiological processes relate to changes in RI in ASD and in how far these processes are affected by possible multisensory integration deficits in ASD. METHOD: Combining high-density EEG recordings with source localization analyses, we examined a group of adolescent ASD patients (n = 20) and healthy controls (n = 20) using a novel RI task. RESULTS: Compared to controls, RI processes are generally compromised in adolescent ASD. This aggravation of RI processes is modulated by the content of multisensory information. The neurophysiological data suggest that deficits in ASD emerge in attentional selection and resource allocation processes related to occipito-parietal and middle frontal regions. Most importantly, conflict monitoring subprocesses during RI were specifically modulated by content of multisensory information in the superior frontal gyrus. CONCLUSIONS: RI processes are overstrained in adolescent ASD, especially when conflicting multisensory information has to be integrated to perform RI. It seems that the content of multisensory input is important to consider in ASD and its effects on cognitive control processes.

Real-time monitoring of CdTe quantum dots growth in aqueous solution.

Quantum dots (QDs) are remarkable semiconductor nanoparticles, whose optical properties are strongly size-dependent. Therefore, the real-time monitoring of crystal growth pathway during synthesis gives an excellent opportunity to a smart design of the QDs luminescence. In this work, we present a new approach for monitoring the formation of QDs in aqueous solution up to 90 °C, through in situ luminescence analysis, using CdTe as a model system. This technique allows a detailed examination of the evolution of their light emission. In contrast to in situ absorbance analysis, the in situ luminescence measurements in reflection geometry are particularly advantageous once they are not hindered by the concentration increase of the colloidal suspension. The synthesized particles were additionally characterized using X-ray diffraction analysis, transition electron microscopy, UV-Vis absorption and infrared spectroscopy. The infrared spectra showed that 3-mercaptopropionic acid (MPA)-based thiols are covalently bound on the surface of QDs and microscopy revealed the formation of CdS. Setting a total of 3 h of reaction time, for instance, the QDs synthesized at 70, 80 and 90 °C exhibit emission maxima centered at 550, 600 and 655 nm. The in situ monitoring approach opens doors for a more precise achievement of the desired emission wavelength of QDs.

Functional NiTi grids for in situ straining in the TEM.

In situ measurements are a pivotal extension of conventional transmission electron microscopy (TEM). By means of the shape memory alloy NiTi thin film Functional Grids were produced for in situ straining as alternative or at least complement of expensive commercial holders. Due to the martensite-austenite transition temperature straining effects can be observed by use of customary heating holders in the range of 50 to 100°C. The grids can be produced in diversified designs to fit for different strain situations. Micro tensile tests were performed and compared with finite element simulations to estimate the applied forces on the sample and to predict the functionality of different grid designs. As a first example of this Functional Grid technology, we demonstrate the impact of applying a strain to a network of ZnO tetrapods.

Structural characterization of the LEM motif common to three human inner nuclear membrane proteins.

BACKGROUND: Integral membrane proteins of the inner nuclear membrane are involved in chromatin organization and postmitotic reassembly of the nucleus. The discovery that mutations in the gene encoding emerin causes X-linked Emery-Dreifuss muscular dystrophy has enhanced interest in such proteins. A common structural domain of 50 residues, called the LEM domain, has been identified in emerin MAN1, and lamina-associated polypeptide (LAP) 2. In particular, all LAP2 isoforms share an N-terminal segment composed of such a LEM domain that is connected to a highly divergent LEM-like domain by a linker that is probably unstructured. RESULTS: We have determined the three-dimensional structures of the LEM and LEM-like domains of LAP2 using nuclear magnetic resonance and molecular modeling. Both domains adopt the same fold, mainly composed of two large parallel alpha helices. CONCLUSIONS: The structural LEM motif is found in human inner nuclear membrane proteins and in protein-protein interaction domains from bacterial multienzyme complexes. This suggests that LEM and LEM-like domains are protein-protein interaction domains. A region conserved in all LEM domains, at the surface of helix 2, could mediate interaction between LEM domains and a common protein partner.

Interference with the constitutive activation of ERK1 and ERK2 impairs EWS/FLI-1-dependent transformation.

The chimeric gene EWS/FLI-1, the hallmark of the Ewing's sarcoma and primitive neuroectodermal tumor family, encodes a fusion protein with enhanced transcriptional activation properties and preserved recognition of canonical ETS binding sites. Although EWS/FLI-1 alters the expression of various genes, the precise mechanism by which EWS/FLI-1 acts as an oncogene remains to be defined. In this study we report that members of the mitogen-activated protein kinase (MAPK) signaling pathway, ERK1 and ERK2, are constitutively activated in NIH 3T3 cells expressing EWS/FLI-1. Interference with ERK activation by either highly specific inhibitors of MEK1 or a dominant negative ras mutant profoundly impaired the ability of EWS/FLI-1 to transform NIH3T3 cells to growth in semi-solid medium. An EWS/FLI-1 mutant defective in DNA-binding and transcriptional activation failed to activate ERK and was also defective in 3T3 cell transformation. Constitutive ERK activation was also evident in several human Ewing's sarcoma tumor-derived cell lines. Interestingly, cells expressing the type II EWS/FLI-1 fusion, recently demonstrated more potent in transcriptional activation, showed even greater MAPK activation than cells expressing the more common type I fusion. These results implicate ERK activation in EWS/FLI-1 transformation and suggest that this signaling pathway may be important in the pathogenesis of Ewing's sarcoma. Oncogene (2000) 19, 4523 - 4530.

Getting the cost right in cost-effectiveness analyses.

OBJECTIVE: The authors examined different ways of measuring unit costs and how methodological assumptions can affect the magnitude of cost estimates and the ratio of treatment costs in comparative studies of mental health interventions. Four methodological choices may bias cost estimates: study perspective, definition of the opportunity cost of resources, cost allocation rules, and measurement of service units. METHOD: Unit costs for outpatient services, individual therapy, and group therapy were calculated under different assumptions for a single community mental health center (CMHC). Using hypothetical service utilization profiles, the authors used the unit costs to calculate the costs of mental health treatments provided by two programs of the CMHC. RESULTS: The unit costs for an hour of outpatient services ranged from $108 to $538. The unit costs for an hour of therapy varied by 156%; unit costs were lowest if the management perspective was assumed and highest if the economist perspective was assumed. The ratio of the outpatient costs in the two treatment programs ranged from 0.6 to 1.8. CONCLUSIONS: The potential errors introduced by methodological choices can bias cost-effectiveness findings based on randomized control trials. These errors go undetected because crucial methodological information is not reported.

Day hospital/crisis respite care versus inpatient care, Part II: Service utilization and costs.

OBJECTIVE: The authors compared service utilization and costs for acutely ill psychiatric patients treated in a day hospital/crisis respite program or in a hospital inpatient program. METHOD: The patients (N = 197) were randomly assigned to one of the two programs and followed for 10 months after discharge. Both programs were provided by a community mental health center (CMHC) in a poor urban community. Data were collected for developing service utilization profiles and estimates of per-unit costs of the inpatient, day hospital, and outpatient services provided by the CMHC. RESULTS: On average, the day hospital/crisis respite program cost less than inpatient hospitalization. The average saving per patient was +7,100, or roughly 20% of the total direct costs. There were no significant differences between programs in service utilization or costs during the follow-up phase. Cost savings accrued in the index episode because per-unit costs were lower for day hospital/crisis respite and the average stay was shorter. Significant differences in cost were found among patient groups with psychosis, affective disorders, and dual diagnoses; psychotic patients had the highest costs in both programs. The two programs had roughly equal direct service staff and capital costs but significantly different operating costs (day hospital/crisis respite operating costs were 51% of inpatient hospital costs). CONCLUSIONS: The programs were equally effective, but day hospital/crisis respite treatment was less expensive for some patients. Potential cost savings are higher for nonpsychotic patients. Cost differences between the programs are driven by the hospital's relatively higher overhead costs. The roughly equal expenditures for direct service staff costs in the two programs may be an important clue for understanding why these programs provided equally effective acute care.

Cost-effectiveness evaluation of three approaches to case management for homeless mentally ill clients.

OBJECTIVE: In this study the authors compared the cost-effectiveness of three approaches to case management for individuals with severe mental illness who were at risk for homelessness: assertive community treatment alone, assertive community treatment with community workers, and brokered case management (purchase of services). METHOD: Individuals were randomly assigned to the three treatment conditions and followed for 18 months. Eligibility requirements included a severe DSM-III axis I diagnosis, such as schizophrenia, and either current homelessness or risk for homelessness based on prior history of homelessness. Participants were recruited from the emergency rooms and inpatient units of local psychiatric hospitals. Data on 85 people were available for analyses: 28 in assertive community treatment alone, 35 in assertive community treatment with community workers, and 22 receiving brokered case management (purchase of services). RESULTS: Clients assigned to the two assertive community treatment conditions had more contact with their treatment programs, experienced greater reductions in psychiatric symptoms, and were more satisfied with their treatment than clients in the brokered condition. There was no statistically significant difference between treatment conditions in terms of the total costs of treating the participants. However, the assertive community treatment conditions spent less money on inpatient services than brokered case management, but more on case management services and maintenance (i.e., food stamps, housing subsidies, and Supplemental Security Income payments). CONCLUSIONS: Assertive community treatment has better client outcomes at no greater cost and is, therefore, more cost-effective than brokered case management.

Expression cloning and characterization of a renal organic anion transporter from winter flounder.

The cDNA coding for a renal p-aminohippurate (PAH) transporter from winter flounder (Pseudopleuronectes americanus), designated fROAT, was cloned by functional expression in Xenopus laevis oocytes. fROAT is approximately 2.8 kbp in length and encodes a protein of 562 amino acids, related to the rat renal organic anion transporter ROAT1/OAT1 and the organic cation transporters OCT1 and OCT2. In oocytes, fROAT mediated probenecid-sensitive PAH uptake, with a Km for PAH of about 20 microM, and inhibited by external glutarate (GA) (1 mM). The functional characteristics suggest that fROAT is the basolateral PAH/dicarboxylate exchanger of the flounder kidney.

Structural analysis of emerin, an inner nuclear membrane protein mutated in X-linked Emery-Dreifuss muscular dystrophy.

Like Duchenne and Becker muscular dystrophies, Emery-Dreifuss muscular dystrophy (EDMD) is characterized by myopathic and cardiomyopathic abnormalities. EDMD has the particularity of being linked to mutations in nuclear proteins. The X-linked form of EDMD is caused by mutations in the emerin gene, whereas autosomal dominant EDMD is caused by mutations in the lamin A/C gene. Emerin colocalizes with lamin A/C in interphase cells, and binds in vitro to lamin A/C. Recent work suggests that lamin A/C might serve as a receptor for emerin. We have undertaken a structural analysis of emerin, and in particular of its N-terminal domain, which is comprised in the emerin segment critical for binding to lamin A/C. We show that region 2-54 of emerin adopts the LEM fold. This fold was originally described in the two N-terminal domains of another inner nuclear membrane protein called lamina-associated protein 2 (LAP2). The existence of a conserved solvent-exposed surface on the LEM domains of LAP2 and emerin is discussed, as well as the nature of a possible common target.

Tumor cells in blood shed from the surgical field.

OBJECTIVES: To analyze blood shed from the surgical field during oncologic surgery for tumor cells and to assess functional characteristics of these cells. DESIGN AND PATIENTS: Series of 61 patients with cancer who underwent surgery for an abdominal, orthopedic, urological, gynecological, or head and neck malignant tumor, and blinded comparison with 15 patients with benign diseases undergoing surgery. SETTING: A 500-bed tumor center and a tertiary care hospital. MAIN OUTCOME MEASURES: Tumor cells were isolated from intraoperatively salvaged and washed blood by density gradient centrifugation. They were identified in cytospin specimens by their content of cytokeratins and nucleolar organizer regions with a sensitivity of 10 cells in 500 mL of blood. Clonogenicity was tested in a cell colony assay; invasiveness, in Boyden chambers; and tumorigenicity, in nude mice. RESULTS: In 57 of 61 patients, tumor cells were detected in the blood shed during oncologic surgery. They demonstrated proliferation capacity, invasiveness, and tumorigenicity. The total number of tumor cells identified ranged from 1 x 10(1) to 7 x 10(6), with no close correlation to the amount of blood loss. Circulating tumor cells were demonstrated in only 26% of these patients and in small numbers. CONCLUSIONS: Malignant cells identified regularly in the blood shed during tumor surgery and different from circulating tumor cells are of concern, since at the surgical site they may cause local tumor recurrence, or in the salvaged blood they may cause hematogenic metastasis after retransfusion. Therefore, the contraindication of intraoperative autotransfusion in tumor surgery is strongly supported, and a review of surgical procedures and adjuvant therapy may be indicated, as the passage of the identified cells to the shed blood is yet unknown.

Professional uncertainty and physician medical decision-making in a multiple treatment framework.

This paper develops a new microanalytic approach to physician medical decision-making treatment setting. Physician medical decision-making is modelled as a two-stage sequential process. In Stage 1, the patient's illness is diagnosed and the health outcomes for all illness-related restoration options are identified. In Stage 2, an "optimal" restoration option is selected. This model provides new insights into physician medical decision-making and the complexity of proving physician-induced demand in a medical care market where professional uncertainty and consumer heterogeneity exist.

Risk, motives, and styles of utilization review: a cross-condition comparison.

In the United States various forms of managed care have been introduced to control the use of expensive medical services. One of the most prominent involves utilization review of hospital admissions. While reviewing the appropriateness of inpatient treatment is appealing in principle, its application is made difficult by clinical uncertainty. Managed care plans develop and implement review criteria often without the guidance of clear clinical norms of treatment. Under these conditions, we suggest that utilization review organizations (UROs) can be expected to develop "styles" of review that respond to clinical uncertainty, influenced by their experience, professional orientation, and financial incentives. Two review styles are explored in this paper: standardization, where the URO reduces the variance in clinical practices by eliminating those practices that deviate from professional norms and stringency, whereby the URO shifts the distribution of clinical practice as it tries to change the professional norms of practice. Data from a 1992-1993 national survey of utilization review organizations are used to test whether UROs have review styles that systematically respond to organizational attributes, economic pressures, and clinical uncertainty associated with three medical conditions: cardiac catheterization, low back pain, and adolescent depression. UROs were found to adopt more stringent review strategies for conditions with weaker norms of appropriate treatment. Financial incentives and organizational experience are positively related to greater stringency. Standardization responds to professional orientation and organizational experience. Variation in the review styles of UROs has implications for the resulting distribution of clinical practices as well as the equity of access to medical care.

Treatment patterns for schizophrenia in psychiatric hospitals.

This paper analyzes the patterns of clinical treatments prescribed to patients diagnosed with schizophrenia who were admitted to state and county mental hospitals, private for-profit psychiatric hospitals, and private nonprofit psychiatric hospitals in July 1980. Treatment patterns were specified by examining the distribution of treatment types provided to patients over a 3-month period through standard tabular arrays and matrix analysis that holds constant the number of treatment types received by the patients. Data for this study are based on nationwide patient sample surveys and facility enumerations conducted in 1980 by the Survey and Reports Branch, National Institute of Mental Health. Clear differences and similarities emerged among the three types of hospitals in terms of the number and type of treatments provided to patients with schizophrenia. In general, patients with schizophrenia admitted to private psychiatric hospitals received a more comprehensive care regimen (generally inclusive of individual therapy) than similarly diagnosed patients admitted to state and county mental hospitals; private nonprofit psychiatric hospitals had marginally discernible treatment patterns from private for-profit psychiatric hospitals, especially with respect to assignment of group and self-care skill training.