Platelet Count and Volume and Pharmacological Closure with Paracetamol of Ductus Arteriosus in Preterm Infants

Background: Low platelet count might promote resistance to pharmacological closure with indomethacin and ibuprofen of a hemodynamically significant patent ductus arteriosus (hsPDA). However, no studies have investigated if this occurs with paracetamol. Methods: We retrospectively assessed the correlation between platelet count, mean platelet volume (MPV), and plateletcrit (PCT), as well as the effectiveness of paracetamol in closing hsPDA in infants born at 23+0 –31+6 weeks of gestation who were treated with 15 mg/kg/6 h of i.v. paracetamol for 3 days. Results: We studied 79 infants: 37 (47%) Had closure after a course of paracetamol and 42 (53%) did not. Platelet count and PCT did not correlate with paracetamol success or failure in closing hsPDA, while MPV was lower at birth (10.7 ± 1.4 vs. 9.5 ± 1.1; p < 0.001) and prior to starting therapy (11.7 ± 1.9 vs. 11.0 ± 1.6; p = 0.079) in refractory infants. Regression analysis confirmed that the low MVP measured prior to starting the treatment increased the risk of hsPDA paracetamol closure failure (OR 1.664, 95% CI 1.153–2.401). Conclusions: The greater MPV correlated positively with the effectiveness of paracetamol in closing hsPDA, while platelet count and PCT did not influence closure rates. Additional studies are needed to confirm our results

Pressure Induced Topological Phase Transitions in Membranes

Some highly unusual features of a lipid-water liquid crystal are revealed by high pressure x-ray diffraction, light scattering and dilatometric studies of the lamellar (bilayer $L_{\alpha}$) to nonlamellar inverse hexagonal ($H_{II}$) phase transition. (i) The size of the unit cell of the $H_{II}$ phase increases with increasing pressure. (ii) The transition volume, $\Delta V_{bh}$, decreases and appears to vanish as the pressure is increased. (iii) The intensity of scattered light increases as $\Delta V_{bh}$ decreases. Data are presented which suggest that this increase is due to the formation of an intermediate cubic phase, as predicted by recent theoretical suggestions of the underlying universal phase sequence.Comment: 12 pages, typed using REVTEX 2.

How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease-decision analysis and comparison of three international patient populations.

Abstract BACKGROUND: We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on www.PATHFx.org , we attempted to externally validate it using independent, international data. METHODS: We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2010 and 2013, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). RESULTS: The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. CONCLUSIONS: PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied

Tick-borne encephalitis in north-east Italy: a 14-year retrospective study, January 2000 to December 2013

Italy is considered at low incidence of tick-borne encephalitis (TBE), and the occurrence of human cases of TBE appears to be geographically restricted to the north east of the country. However, most information to date derives from case series, with no systematic data collection. To estimate incidence rates (IR) and spatial distribution of TBE cases, we conducted a retrospective study in north-eastern Italy. Data were collected through the infectious disease units and public health districts of three regions (Friuli Venezia Giulia, Trentino Alto Adige and Veneto) between 2000 and 2013. Overall, 367 cases were identified (IR: 0.38/100,000). The cases' median age was 56 years and 257 (70%) were male. Central nervous system involvement was reported in 307 cases (84%). Annual fluctuations in case numbers occurred, with peaks in 2006 and in 2013, when 44 and 42 cases were respectively observed. A strong seasonality effect was noted, with the highest number of cases in July. In terms of geographical location, three main endemic foci with high TBE IR (> 10/100,000) were identified in three provinces, namely Belluno (Veneto region), Udine (Friuli Venezia Giulia) and Trento (Trentino Alto-Adige). When investigating the whole study area in terms of altitude, the IR between 400 and 600\u2009m was greater (2.41/100,000) than at other altitudes (p< 0.01). In conclusion, the incidence of TBE in Italy is relatively low, even considering only the three known affected regions. However, three endemic foci at high risk were identified. In these areas, where the risk of TBEV infection is likely high, more active offer of TBE vaccination could be considere

Strong-Segregation Theory of Bicontinuous Phases in Block Copolymers

We compute phase diagrams for $A_nB_m$ starblock copolymers in the strong-segregation regime as a function of volume fraction $\phi$, including bicontinuous phases related to minimal surfaces (G, D, and P surfaces) as candidate structures. We present the details of a general method to compute free energies in the strong segregation limit, and demonstrate that the gyroid G phase is the most nearly stable among the bicontinuous phases considered. We explore some effects of conformational asymmetry on the topology of the phase diagram.Comment: 14 pages, latex, 21 figures, to appear in Macromolecule

Crystallizing membrane proteins using lipidic mesophases

peer-reviewedThis paper was obtained through PEER (Publishing and the Ecology of European Research) http://www.peerproject.euA detailed protocol for crystallizing membrane proteins that makes use of lipidic mesophases is described. This has variously been referred to as the lipid cubic phase or in meso method. The method has been shown to be quite general in that it has been used to solve X-ray crystallographic structures of prokaryotic and eukaryotic proteins, proteins that are monomeric, homo- and hetero-multimeric, chromophore-containing and chromophore-free, and α-helical and β-barrel proteins. Its most recent successes are the human engineered β2-adrenergic and adenosine A2A G protein-coupled receptors. Protocols are provided for preparing and characterizing the lipidic mesophase, for reconstituting the protein into the monoolein-based mesophase, for functional assay of the protein in the mesophase, and for setting up crystallizations in manual mode. Methods for harvesting micro-crystals are also described. The time required to prepare the protein-loaded mesophase and to set up a crystallization plate manually is about one hour

Long-lived photoexcited states in polydiacetylenes with different molecular and supramolecular organization

With the aim of determining the importance of the molecular and supramolecular organization on the excited states of polydiacetylenes, we have studied the photoinduced absorption spectra of the red form of poly[1,6-bis(3,6-didodecyl-N-carbazolyl)-2,4-hexadiyne] (polyDCHD-S) and the results compared with those of the blue form of the same polymer. An interpretation of the data is given in terms of both the conjugation length and the interbackbone separation also in relation to the photoinduced absorption spectra of both blue and red forms of poly[1,6-bis(N-carbazolyl)-2,4-hexadiyne] (polyDCHD), which does not carry the alkyl substituents on the carbazolyl side groups. Information on the above properties is derived from the analysis of the absorption and Raman spectra of this class of polydiacetylenes

Monoolein Lipid Phases as Incorporation and Enrichment Materials for Membrane Protein Crystallization

The crystallization of membrane proteins in amphiphile-rich materials such as lipidic cubic phases is an established methodology in many structural biology laboratories. The standard procedure employed with this methodology requires the generation of a highly viscous lipidic material by mixing lipid, for instance monoolein, with a solution of the detergent solubilized membrane protein. This preparation is often carried out with specialized mixing tools that allow handling of the highly viscous materials while minimizing dead volume to save precious membrane protein sample. The processes that occur during the initial mixing of the lipid with the membrane protein are not well understood. Here we show that the formation of the lipidic phases and the incorporation of the membrane protein into such materials can be separated experimentally. Specifically, we have investigated the effect of different initial monoolein-based lipid phase states on the crystallization behavior of the colored photosynthetic reaction center from Rhodobacter sphaeroides. We find that the detergent solubilized photosynthetic reaction center spontaneously inserts into and concentrates in the lipid matrix without any mixing, and that the initial lipid material phase state is irrelevant for productive crystallization. A substantial in-situ enrichment of the membrane protein to concentration levels that are otherwise unobtainable occurs in a thin layer on the surface of the lipidic material. These results have important practical applications and hence we suggest a simplified protocol for membrane protein crystallization within amphiphile rich materials, eliminating any specialized mixing tools to prepare crystallization experiments within lipidic cubic phases. Furthermore, by virtue of sampling a membrane protein concentration gradient within a single crystallization experiment, this crystallization technique is more robust and increases the efficiency of identifying productive crystallization parameters. Finally, we provide a model that explains the incorporation of the membrane protein from solution into the lipid phase via a portal lamellar phase