Design, synthesis, and conformational analysis of 3-cyclo-butylcarbamoyl hydantoins as novel hydrogen bond driven universal peptidomimetics.

A collection of systematically substituted 3-cyclo-butylcarbamoyl hydantoins was synthesized by a regioselective multicomponent domino process followed by easy coupling reactions. Calculations, NMR studies and X-ray analysis show that these scaffolds are able to project their side chains similar to common secondary structures, such as the α-helix and ß-turn, with favourable enthalpic and entropic profiles.

Differentiation and adaptive radiation of amphibious gobies (Gobiidae: Oxudercinae) in semi-terrestrial habitats.

During several surveys made in the region of the lower Fly River and delta, Papua New Guinea, nine species of oxudercine gobies (Gobiidae: Oxudercinae) were recorded: Boleophthalmus caeruleomaculatus, Oxuderces wirzi, Periophthalmodon freycineti, Periophthalmus darwini, Periophthalmus novaeguineaensis, Periophthalmus takita, Periophthalmus weberi, Scartelaos histophorus and Zappa confluentus. An exploratory multivariate analysis of their habitat conditions discriminated five guilds, differentially distributed in habitats with different quantities of environmental water and three guilds corresponding to different levels of salinity. A partial correspondence between phylogenetic and ecological categories suggested the presence of parallel adaptive radiations within different genera. In particular, the species found in the most terrestrial habitats (P. weberi) was also found in the widest range of conditions, suggesting that colonization of extreme semi-terrestrial and freshwater habitats by this species was facilitated by eurytypy. It is proposed that these findings provide insight into convergent adaptations for the vertebrate eco-evolutionary transition from sea to land.

The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma.

Genomic translocations have been implicated in cancer. In this study, we performed a screen for genetic translocations in gliomas based on exon-level expression profiles. We identified a translocation in the contactin-associated protein-like 2 (CASPR2) gene, encoding a cell adhesion molecule. CASPR2 mRNA was fused to an expressed sequence tag that likely is part of the nuclear receptor coactivator 1 gene. Despite high mRNA expression levels, no CASPR2 fusion protein was detected. In a set of 25 glioblastomas and 22 oligodendrogliomas, mutation analysis identified two additional samples with genetic alterations in the CASPR2 gene and all three identified genetic alterations are likely to reduce CASPR2 protein expression levels. Methylation of the CASPR2 gene was also observed in gliomas and glioma cell lines. CASPR2-overexpressing cells showed decreased proliferation rates, likely because of an increase in apoptosis. Moreover, high CASPR2 mRNA expression level is positively correlated with survival and is an independent prognostic factor. These results indicate that CASPR2 acts as a tumor suppressor gene in glioma.

Melting of the Na layers in solid Na0.8CoO2.

Data of 23Na NMR spectra and relaxation measurements are interpreted as suggesting that, upon increasing temperature, the Na layers in Na0.8CoO2 adopt a 2D liquid state at T=291 K. The corresponding first order phase transition is preceded by a rapidly increasing mobility and diffusion of Na ions above 200 K. Above 291 K, the 23Na NMR response is similar to that previously observed in superionic conductors with planar Na layers.

[Health-related quality of life in patients with chronic kidney disease]. / Qualita' della vita nei nefropatici.

Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment.

Pressure dependence of the charge-density-wave gap in rare-earth tritellurides.

We investigate the pressure dependence of the optical properties of CeTe3, which exhibits an incommensurate charge-density-wave (CDW) state already at 300 K. Our data are collected in the midinfrared spectral range at room temperature and at pressures between 0 and 9 GPa. The energy for the single particle excitation across the CDW gap decreases upon increasing the applied pressure, similarly to the chemical pressure by rare-earth substitution. The broadening of the bands upon lattice compression removes the perfect nesting condition of the Fermi surface and therefore diminishes the impact of the CDW transition on the electronic properties of RTe3.

The safety of single-physician procedural sedation in the emergency department.

BACKGROUND: Previous research has shown the safety of procedural sedation in the emergency department in university settings involving multiple emergency physicians. OBJECTIVE: To examine sedation in the emergency department conducted by a single emergency physician with monitoring by the emergency nurse. METHODS: The Procedural Sedation in the Community Emergency Department Registry is a prospective observational database of procedural sedation cases directed by the emergency physicians. Among other parameters, the registry tracts whether emergency physicians or emergency nurses monitored patient sedation. The incidence of complications and outcomes were compared between these two monitoring groups. RESULTS: 1028 procedural sedations were performed on 977 patients at 14 sites. In 885 (86.1%) cases the emergency physician directed the sedation, and performed the procedure with monitoring by the emergency nurse. Complications occurred in 42 (4.1%) patients, 35 (4.0%) EN monitored patients and 6 (4.2%) EP monitored patients (p>0.7). Procedures were successful in 863 (97.5%) cases monitored by emergency nurses and in 140 (97.9%) patients monitored by emergency physicians (p>0.7). CONCLUSION: Procedural sedation in the emergency department performed by a single emergency physician is safe and effective.

Far-infrared absorption of La1-xCaxMnO3-y at high pressure.

The first far-infrared absorption spectra of manganite samples at pressures P up to 10 GPa were obtained on La1-xCaxMnO3-y by use of synchrotron radiation. For x=0.25 and 0.20 (y=0), P promotes partial metallization at room temperature through a strong reduction of the insulating gap. An x=0.20 sample with y=0.08 does not show any charge delocalization effect up to 10 GPa. An Urbach-like model of disordered Jahn-Teller wells is shown to well fit the far-infrared band edge and allows one to obtain a reliable pressure dependence of the energy gap.

A comparative EPR, infrared and Raman study of natural and deproteinated tooth enamel and dentin.

The aim of the present work was to investigate how the native signal observed in the electron paramagnetic resonance (EPR) spectrum of tooth enamel and dentin is associated with the organic content of the two tissues. This was achieved by comparing the EPR native signal and the optical bands (Raman and infrared, IR) associated with organic components of tooth enamel and dentin, in natural and deproteinated samples. The main results were: (a) in natural samples, the organic optical bands are more intense in dentin than in enamel, in contrast with the EPR native signal which shows similar intensity in the two tissues; (b) after deproteination, the optical organic bands are completely suppressed in both dentin and enamel, while the EPR native signal is eliminated only in dentin. It is suggested that the IR and Raman organic bands are originated in the bulk of the organic matrix, while the paramagnetic centres associated with the EPR native signal are located in the organic-mineral interface.

Hypoventilation and hypoxia in reversal of cardiogenic shock in an infant with congenital heart disease.

The case is presented of a child in cardiogenic shock in whom oxygen administration exacerbated a systemic to pulmonary shunt that caused a critical deterioration in his cardiovascular status requiring hypoventilation and restoration of baseline hypoxia for reversal.

[Evaluation of quality of life by improving the uraemic anaemia status]. / Miglioramento dello stato anemico e valutazione della qualita' di vita del paziente in trattamento dialitico sostitutivo. Applicazione del ciclo dell'"audit" ad una unita' di nefrologia e dialisi.

BACKGROUND: Anaemia is one of the most common signs of chronic uraemia that determines an increase in both morbidity and mortality, as well as a deterioration in the quality of life of affected patients. We evaluated the impact of the application of the European Best Practice Anaemia Guidelines to the quality of life of dialysed patients. PATIENTS AND METHODS: We studied for 12 months (from December 2000 to November 2001) 62 patients in haemodialysis and 22 patients in peritoneal dialysis. For the statistical analysis the following parameters were examined: haemoglobin levels, TSAT, and weekly doses of Epo. To assess the quality of life we asked the patients, at the initial visit and 12 months after treatment, to fill out the "Medical Outcome Study Short Form 36 items Heath Survey" and "Kidney Disease Quality of Life". RESULTS: The significant increase in TSAT levels attained in haemodialysed patients (p = 0.03) induced an increase in haemoglobin levels and consequent reduction in EPO administration (p = 0.04). During the study, a significant improvement in General Health (GH) (p = 0.03) was observed. At the end of the treatment, Physical Functioning (PF) (p = 0.04), Role and Physical Health (RP) (p = 0.02) and Social Functioning (SF) (p = 0.005) showed significant variations. CONCLUSIONS: The application of the European Best Practice Anaemia Guidelines improves the management of anaemia and the Global Health Assessment in uraemic patients. These data demonstrate how inappropriate anaemia management can negatively affect the quality of life of these patients and increase the medical costs.

Pressure tuning of electron-phonon coupling: the insulator to metal transition in manganites.

An extended temperature and pressure-dependent investigation is carried out on a La0.75Ca0.25MnO3 sample exploiting the infrared absorption technique coupled to a diamond anvil cell. The pressure dependence of the insulator to metal transition temperature T(IM) is determined for the first time up to 11.2 GPa. The T(IM)(P) curve we propose to model the present data has an exponential-like behavior with an associated characteristic pressure P* playing the role of a decay constant. It is found that the equivalence between an external and an internal (chemical) pressure holds over a limited range of pressure, namely, P< or =2P*. Moreover, a certain universality character is associated with the proposed model curve in its ability to account for a large class of low-disorder manganites characterized by intermediate electron-phonon coupling.

[Child sexual abuse primary prevention: outcome evaluation of a health education project implemented in Milan's elementary schools]. / Prevenzione primaria dell'abuso sessuale all'infanzia. Valutazione di efficacia di un progetto di educazione alla salute realizzato nelle scuole elementari di Milano.

The study we present is aimed at evaluating the efficacy of a child sexual abuse prevention program that involved children attending 4th and 5th grade in Milan's (Italy) elementary schools. The project involved 53 classes (10 of 4th, 43 of 5th grade) during school year 2000-2001. Children filled a questionnaire before the beginning of the project and two months after the end; the questionnaire evaluates children's perception of risk and their self-efficacy skills in adopting protective strategies when involved in at risk situations. Final analysis has involved 674 children, 51.8% girls, 48.2% boys; 19.6% of children attended 4th grade, 80.4% 5th grade. Percentage of children that recognize the potential danger in the suggested at-risk situation is higher in post-test then in pre-test (87.9% vs 73.2%) and the number of them that does not adopt any self-defence strategy decreases (from 35.3% to 21.0%). The project increased the number of children that know body puberal changes (from 16.0% to 32.8%). According to these results it is evident that the program increased children's capacity to recognize and use self defence strategies in at risk situations. These results call for a potential extention and replication of this health education program.

Green fluorescent protein variants fold differentially in prokaryotic and eukaryotic cells.

Better-folding Green Fluorescent Protein (GFP) mutants selected from bacterial screenings are commonly used in widely different cellular environments. However, it is unclear if the folding efficiency of GFPs is invariant in different cell types. In this work, we have analysed the folding properties of GFP variants in bacteria versus mammalian cells. Remarkably, S65T was found to fold at comparable levels with the wild type GFP in bacteria, but at 10-fold lower levels in mammalian cells. On the other hand, Bex1 folded 3-4 times better than the wtGFP or S65T in E. coli, and 10-20-fold or more than 95-fold better, respectively, in mammalian cells. The Vex1 mutant demonstrated similar properties to Bex1. No evidence of differential GFP unfolding in vivo or of preferential degradation of unfolded GFP molecules was found. Moreover, no relationship between GFP folding efficiency and expression levels, or protein stability was detected. Trivial Aconfounding factors, like GFP unfolding caused by different pH or fluorescence quenching due to molecular crowding, were also excluded. In summary, our results demonstrate that specific GFP variants follow different folding trajectories in mammalian versus bacterial cells. The specificity of this differential folding supports a role of chaperones in guiding the folding of GFP in vivo. J. Cell. Biochem. Suppl. 36: 117-128, 2001.

Efficient GFP mutations profoundly affect mRNA transcription and translation rates.

Green fluorescent protein (GFP) variants with higher expression efficiencies have been generated by mutagenesis. Favorable mutations often improve the folding of GFP. However, an effect on protein folding fails to explain the efficiency of several other GFP mutations. In this work, we demonstrate that mutations of the GFP open reading frame and untranslated regions profoundly affect mRNA transcription and translation efficiencies. The removal of the GFP 5' untranslated region halves the transcription rate of the GFP gene, but hugely improves its translation rate. Mutations of the GFP open reading frame or the addition of peptide sequences differentially reduce the GFP mRNA transcription rate, translation efficiency and protein stability. These previously unrecognized effects are demonstrated to be critical to the efficiency of GFP mutants. These findings indicate the feasibility of generating more efficient GFP variants, with optimized mRNA transcription and translation in eukaryotic cells.

Utility of UB-92 data for monitoring emergency department performance improvement.

The Universal Billing Code of 1992 (UB-92) is a standard database used by hospitals to generate itemized charges for patient visits. This study examined the use of UB-92 information to monitor emergency department performance improvement projects. UB-92 data were used to determine whether urine tests had been ordered for emergency department patients. A population of patients at low risk for requiring a urine culture was defined as discharged female patients between 16 and 60 years of age undergoing a urinalysis as part of their emergency department treatment during a 10-month period. Based on UB-92 data, only a total of 2,138 patients were identified who met the study's low-risk criteria. Recommendations for the optimum use of these tests were presented to the emergency physicians as part of departmental performance improvement activities. Additional logistical problems associated with the procedure for ordering this test were identified and corrected as part of this project. After an additional 5-month period, a second analysis of the entire 15 months of UB-92 data was performed. Prior to physician notification, 41.6% of low-risk patients underwent both a urinalysis and a urine culture and sensitivity in the emergency department. In the 5-month follow-up period, the percentage of patients undergoing both tests decreased 18% to only 23%.

The potential for errors in children with special health care needs.

Children with special health care needs (CSHCN) are at risk for suboptimal treatment when presenting for emergent care to unfamiliar health care providers. Errors in their management may stem from failure to recognize occult conditions, lack of familiarity with rare or complex medical problems, or lack of prior knowledge of baseline physical findings. An emergency information form (EIF) that contains patient-specific information on essential diagnostic and therapeutic interventions may provide a ready personal reference for the emergent care of CSHCN. Coupled with the use of medical identification jewelry and an electronic transmission system, an EIF has the potential to eliminate management errors in the care of these patients.

Should pediatric emergency care be decentralized?: an out-of-hospital destination model for critically ill children.

OBJECTIVES: A time-to-initial-stabilization model for out-of-hospital destinations of critically ill children (CICs) was developed. Application of this model to assess the impact of changes in different parameters of an emergency medical services for children (EMSC) system is described. METHODS: A computer model created a 2,500-square-mile community containing ten community hospitals (CHs) and one pediatric critical care center (PCC). Community hospitals capable of providing initial immediate stabilization of CICs were defined as emergency departments accepting pediatrics (EDAPs). Critically ill children were randomly selected in proportion to population densities across the modeled community. Time to initial stabilization (TIS) was defined as the time to arrival at either an EDAP or a PCC or time to arrival at a non-EDAP CH + travel time for a team from the PCC to the non-EDAP CH + preparation/dispatch (P/D) time. The following parameters of the model were varied and their effect on TIS was evaluated: location of CHs, location of PCC, primary destinations for CICs, percent of CHs meeting EDAP standards, out-of-hospital compliance with designated hospitals for CICs, P/D time, and ambulance speed. RESULTS: The computer model selected 1,000 CICs in accordance with the population densities of the community. The scenario with the shortest TIS was one in which every CH achieved EDAP designation (9.8 +/- 0.5 minutes). The scenario with the longest TIS involved a model in which every CIC was transported directly to the PCC (28.6 +/- 0.33 minutes). The number of EDAPs in a community and out-of-hospital compliance with use of EDAPs produced comparable effects on the TIS. Travel speeds had a direct effect on TIS but also exaggerated inefficiencies between scenarios. The P/D time had little effect on the TIS. CONCLUSIONS: An out-of-hospital destination model has been developed with the ability to modify multiple EMSC system variables. Application of this model demonstrates the shortest times to stabilization of critically ill children occur in systems that maximize the number of hospitals that meet EDAP standards and decentralize pediatric emergency care.