The effect of placement and management of intrathecal catheters following accidental dural puncture on the incidence of postdural puncture headache and severity: a retrospective real-world study.

Accidental dural puncture during an attempt to establish labour epidural analgesia can result in postdural puncture headache and long-term debilitating conditions. Epidural blood patch, the gold standard treatment for this headache, is invasive and not always successful. Inserting an intrathecal catheter after accidental dural puncture may prevent postdural puncture headache. We evaluated the effect of intrathecal catheter insertion on the incidence of postdural puncture headache and the need for epidural blood patch and whether duration of intrathecal catheterisation or injection of intrathecal saline affected outcome. Our retrospective study was conducted at two tertiary, university-affiliated medical centres between 2017 and 2022 and included 92,651 epidurals and 550 cases of accidental dural puncture (0.59%); 219 parturients (39.8%) received an intrathecal catheter and 331 (60.2%) a resited epidural. Use of an intrathecal catheter versus resiting the epidural did not decrease the odds of postdural puncture headache, adjusted odds ratio (aOR) (95%CI) 0.91 (0.81-1.01), but was associated with a lower need for epidural blood patch (aOR (95%CI) 0.82 (0.73-0.91), p < 0.001). We found no benefit in leaving in the intrathecal catheter for 24 h postpartum (postdural puncture headache, aOR (95%CI) 1.01 (1.00-1.02), p = 0.015; epidural blood patch, aOR (95%CI) 1.00 (0.99-1.01), p = 0.40). We found an added benefit of injecting intrathecal saline as it decreased the incidence of postdural puncture headache (aOR (95%CI) 0.85 (0.73-0.99), p = 0.04) and the need for epidural blood patch (aOR (95%CI) 0.75 (0.64-0.87), p < 0.001). Our study confirms the benefits of intrathecal catheterisation and provides guidance on how to best manage an intrathecal catheter.

The effect of α-linolenic acid enrichment in perinatal diets in preventing high fat diet-induced SCD1 increased activity and lipid disarray in adult offspring of low density lipoprotein receptor knockout (LDLRKO) mice.

The present study examined the effects of maternal perinatal dietary ALA enrichment on the high fat diet (HFD)-induced lipid disarray in the adult offspring of low density lipoprotein receptor knock-out (LDLRKO) mice. Female LDLRKO mice received, during pregnancy and lactation, isocaloric diets with either corn oil, RD, or flax oil, ALA. The weaning offspring was given a regular chow diet for a washout period of eight weeks, which was followed by HFD for eight weeks. Plasma and liver lipids and SCD1 activity were then analyzed. The HFD-fed RD adult offspring had substantially higher plasma cholesterol levels than the HFD-fed ALA offspring (15.7 versus 9.7 mmole/l, p<0.00001) and non-alcoholic fatty liver disease (NAFLD) (65.0 versus 23.9 mg/g lipids, p<0.00001). Liver lipids oleic acid (OA) content and monounsaturated to saturated fatty acids (MUFA/SAT) ratio, were two times lower in RD compared to ALA (p<0.0001). The threefold HFD-induced SCD1 raised activity (p<0.00001), and OA produced from SA, observed in RD adult offspring were prevented by perinatal ALA. In conclusion, the resilience of SCD1 to HFD- induced increased activity may account for the beneficial effects of perinatal ALA dietary enrichment in preventing NAFLD and hypercholesterolemia from occurring in adult LDLRKO offspring mice.

Solving the Structure and Dynamics of Metal Nanoparticles by Combining X-Ray Absorption Fine Structure Spectroscopy and Atomistic Structure Simulations.

Extended X-ray absorption fine structure (EXAFS) spectroscopy is a premiere method for analysis of the structure and structural transformation of nanoparticles. Extraction of analytical information about the three-dimensional structure and dynamics of metal-metal bonds from EXAFS spectra requires special care due to their markedly non-bulk-like character. In recent decades, significant progress has been made in the first-principles modeling of structure and properties of nanoparticles. In this review, we summarize new approaches for EXAFS data analysis that incorporate particle structure modeling into the process of structural refinement.

Investigation of periodically driven systems by x-ray absorption spectroscopy using asynchronous data collection mode.

We report the development, testing, and demonstration of a setup for modulation excitation spectroscopy experiments at the Inner Shell Spectroscopy beamline of National Synchrotron Light Source - II. A computer algorithm and dedicated software were developed for asynchronous data processing and analysis. We demonstrate the reconstruction of X-ray absorption spectra for different time points within the modulation pulse using a model system. This setup and the software are intended for a broad range of functional materials which exhibit structural and/or electronic responses to the external stimulation, such as catalysts, energy and battery materials, and electromechanical devices.

Homogeneity and elemental distribution in self-assembled bimetallic Pd-Pt aerogels prepared by a spontaneous one-step gelation process.

Multi-metallic aerogels have recently emerged as a novel and promising class of unsupported electrocatalyst materials due to their high catalytic activity and improved durability for various electrochemical reactions. Aerogels can be prepared by a spontaneous one-step gelation process, where the chemical co-reduction of metal precursors and the prompt formation of nanochain-containing hydrogels, as a preliminary stage for the preparation of aerogels, take place. However, detailed knowledge about the homogeneity and chemical distribution of these three-dimensional Pd-Pt aerogels at the nano-scale as well as at the macro-scale is still unclear. Therefore, we used a combination of spectroscopic and microscopic techniques to obtain a better insight into the structure and elemental distribution of the various Pd-rich Pd-Pt aerogels prepared by the spontaneous one-step gelation process. Synchrotron-based extended X-ray absorption fine structure (EXAFS) spectroscopy and high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM) in combination with energy-dispersive X-ray spectroscopy (EDX) were employed in this work to uncover the structural architecture and chemical composition of the various Pd-rich Pd-Pt aerogels over a broad length range. The Pd80Pt20, Pd60Pt40 and Pd50Pt50 aerogels showed heterogeneity in the chemical distribution of the Pt and Pd atoms inside the macroscopic nanochain-network. The features of mono-metallic clusters were not detected by EXAFS or STEM-EDX, indicating alloyed nanoparticles. However, the local chemical composition of the Pd-Pt alloys strongly varied along the nanochains and thus within a single aerogel. To determine the electrochemically active surface area (ECSA) of the Pd-Pt aerogels for application in electrocatalysis, we used the electrochemical CO stripping method. Due to their high porosity and extended network structure, the resulting values of the ECSA for the Pd-Pt aerogels were higher than that for a commercially available unsupported Pt black catalyst. We show that the Pd-Pt aerogels possess a high utilization of catalytically active centers for electrocatalytic applications based on the nanostructured bimetallic framework. Knowledge about the homogeneity and chemical distribution of the bimetallic aerogels can help to further optimize their preparation by the spontaneous one-step gelation process and to tune their electrocatalytic reactivity.

Complex structural dynamics of nanocatalysts revealed in Operando conditions by correlated imaging and spectroscopy probes.

Understanding how heterogeneous catalysts change size, shape and structure during chemical reactions is limited by the paucity of methods for studying catalytic ensembles in working state, that is, in operando conditions. Here by a correlated use of synchrotron X-ray absorption spectroscopy and scanning transmission electron microscopy in operando conditions, we quantitatively describe the complex structural dynamics of supported Pt catalysts exhibited during an exemplary catalytic reaction-ethylene hydrogenation. This work exploits a microfabricated catalytic reactor compatible with both probes. The results demonstrate dynamic transformations of the ensemble of Pt clusters that spans a broad size range throughout changing reaction conditions. This method is generalizable to quantitative operando studies of complex systems using a wide variety of X-ray and electron-based experimental probes.

Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice.

OBJECTIVE: Our objective was to test the contribution of dietary enrichment in essential or saturated fatty acids, in normocaloric diets, on the lipid accumulation and insulin resistance in the adult offspring in a C57Bl6/J mice model. METHODS: Pregnant mothers were fed normocaloric diets containing 6% fat enriched in essential fatty acids (EFA): alpha-linolenic (ALA-18:3, n-3), linoleic (LA-18:2, n-6), or saturated fatty acids (SFA). After a washing-out period with regular diet, the offspring received a high-fat diet before euthanization. RESULTS: Adult mice fed maternal ALA showed lower body weight gain and lower liver fat accumulation, lower HOMA index and lower stearoyl-CoA desaturase (SCD1) activity than those fed maternal SFA. CONCLUSION: The results observed using this novel model suggest that ALA in maternal diet may have the potential to inhibit insulin resistance in adult offspring.

Iodine-induced hyperthyroidism-an old clinical entity that is still relevant to daily ICU practice: a case report.

Objective. Hyperthyroidism has been described as elevated serum free T3 and/or free T4 levels with decreased thyrotropin (TSH) concentrations. The main causes are related to autoimmune and neoplastic pathology. However, it might be caused due to a long-term topical exposure (iodine solution dressing) or by intravenous administration of iodine-containing substances. Both clinical and laboratory features might be presented. The main management is based on interruption of all exposures with iodine solutions and also antithyroid medicine in case of severe laboratory and clinical disturbances. Data Sources. We present a case of iodine-induced hyperthyroidism in a critically ill ICU patient caused by excessive iodine containing antiseptic solution washes and contrast agent administration. The patient was successfully treated by discontinuing iodine exposure and beta-blocker administration. Conclusions. In patients with underlying thyroid gland pathology, thyroid-function tests and clinical observation in the ICU are of critical importance.

Ceftaroline - a cause for neutropenia.

WHAT IS KNOWN AND OBJECTIVE: The US Food and Drug Administration approved ceftaroline in 2010 for the treatment of community-acquired pneumonia and skin and soft-tissue infections. The most common adverse reactions are diarrhoea, nausea and rash. To present the first case of neutropenia directly related to ceftaroline. CASE SUMMARY: A 90-year-old female was given ceftaroline for treatment of a pneumonia complicated by methicillin-resistant Staphylococcus aureus bacteraemia and possible vertebral osteomyelitis. After 25 days of ceftaroline, she developed neutropenia. Ceftaroline was discontinued and her white blood cell count returned to normal within one week. WHAT IS NEW AND CONCLUSION: Although neutropenia is a potential cephalosporin class effect, we present the first case of neutropenia directly related to ceftaroline. Agranulocytosis and neutropenia are rare, yet potentially life-threatening adverse effects of cephalosporins. Healthcare providers should be aware of the potential for ceftaroline to cause neutropenia, particularly in patients treated for greater than two weeks.

Traumatic page kidney induced hypertension in critical care: immediately resolved or long-term resistant problem.

Page kidney is a well-known phenomenon causing hypertension, due to compression of renal parenchyma by a subcapsular hematoma, of either traumatic or non-traumatic origin. The main therapeutic approach is based on surgical approach (nephrectomy or hematoma evacuation) and antihypertensive treatment. In this paper we present a post-traumatic case of Page Kidney in a Critical Care unit. We discuss different therapeutical opportunities to extremely elevated systemic blood pressure resistant to traditional drug therapy.

In situ coarsening study of inverse micelle-prepared Pt nanoparticles supported on γ-Al2O3: pretreatment and environmental effects.

The thermal stability of inverse micelle prepared Pt nanoparticles (NPs) supported on nanocrystalline γ-Al(2)O(3) was monitored in situ under different chemical environments (H(2), O(2), H(2)O) via extended X-ray absorption fine-structure spectroscopy (EXAFS) and ex situ via scanning transmission electron microscopy (STEM). Drastic differences in the stability of identically synthesized NP samples were observed upon exposure to two different pre-treatments. In particular, exposure to O(2) at 400 °C before high temperature annealing in H(2) (800 °C) was found to result in the stabilization of the inverse micelle prepared Pt NPs, reaching a maximum overall size after moderate coarsening of ∼1 nm. Interestingly, when an analogous sample was pre-treated in H(2) at ∼400 °C, a final size of ∼5 nm was reached at 800 °C. The beneficial role of oxygen in the stabilization of small Pt NPs was also observed in situ during annealing treatments in O(2) at 450 °C for several hours. In particular, while NPs of 0.5 ± 0.1 nm initial average size did not display any significant sintering (0.6 ± 0.2 nm final size), an analogous thermal treatment in hydrogen leads to NP coarsening (1.2 ± 0.3 nm). The same sample pre-dosed and annealed in an atmosphere containing water only displayed moderate sintering (0.8 ± 0.3 nm). Our data suggest that PtO(x) species, possibly modifying the NP/support interface, play a role in the stabilization of small Pt NPs. Our study reveals the enhanced thermal stability of inverse micelle prepared Pt NPs and the importance of the sample pre-treatment and annealing environment in the minimization of undesired sintering processes affecting the catalytic performance of nanosized particles.

Quick extended x-ray absorption fine structure instrument with millisecond time scale, optimized for in situ applications.

In order to learn about in situ structural changes in materials at subseconds time scale, we have further refined the techniques of quick extended x-ray absorption fine structure (QEXAFS) and quick x-ray absorption near edge structure (XANES) spectroscopies at beamline X18B at the National Synchrotron Light Source. The channel cut Si (111) monochromator oscillation is driven through a tangential arm at 5 Hz, using a cam, dc motor, pulley, and belt system. The rubber belt between the motor and the cam damps the mechanical noise. EXAFS scan taken in 100 ms is comparable to standard data. The angle and the angular range of the monochromator can be changed to collect a full EXAFS or XANES spectrum in the energy range 4.7-40.0 KeV. The data are recorded in ascending and descending order of energy, on the fly, without any loss of beam time. The QEXAFS mechanical system is outside the vacuum system, and therefore changing the mode of operation from conventional to QEXAFS takes only a few minutes. This instrument allows the acquisition of time resolved data in a variety of systems relevant to electrochemical, photochemical, catalytic, materials, and environmental sciences.

Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).

The synthesis is reported here of two novel series of inhibitors of human NAD(P)H quinone oxidoreductase-1 (NQO1), an enzyme overexpressed in several types of tumor cell. The first series comprises substituted symmetric dicoumarol analogues; the second series contains hybrid compounds where one 4-hydroxycoumarin system is replaced by a different aromatic moiety. Several compounds show equivalent or improved NQO1 inhibition over dicoumarol, both in the presence and in the absence of added protein. Further, correlation is demonstrated between the ability of these agents to inhibit NQO1 and computed binding affinity. We have solved the crystal structure of NQO1 complexed to a hybrid compound and find good agreement with the in silico model. For both MIA PaCa-2 pancreatic tumor cells and HCT116 colon cancer cells, dicoumarol shows the greatest toxicity of all compounds. Thus, we provide a computational, synthetic, and biological platform to generate competitive NQO1 inhibitors with superior pharmacological properties to dicoumarol. This will allow a more definitive study of NQO1 activity in cells, in particular, its drug activating/detoxifying properties and ability to modulate oncoprotein stability.

Ternary Pt/Rh/SnO2 electrocatalysts for oxidizing ethanol to CO2.

Ethanol, with its high energy density, likely production from renewable sources and ease of storage and transportation, is almost the ideal combustible for fuel cells wherein its chemical energy can be converted directly into electrical energy. However, commercialization of direct ethanol fuel cells has been impeded by ethanol's slow, inefficient oxidation even at the best electrocatalysts. We synthesized a ternary PtRhSnO(2)/C electrocatalyst by depositing platinum and rhodium atoms on carbon-supported tin dioxide nanoparticles that is capable of oxidizing ethanol with high efficiency and holds great promise for resolving the impediments to developing practical direct ethanol fuel cells. This electrocatalyst effectively splits the C-C bond in ethanol at room temperature in acid solutions, facilitating its oxidation at low potentials to CO(2), which has not been achieved with existing catalysts. Our experiments and density functional theory calculations indicate that the electrocatalyst's activity is due to the specific property of each of its constituents, induced by their interactions. These findings help explain the high activity of Pt-Ru for methanol oxidation and the lack of it for ethanol oxidation, and point to the way to accomplishing the C-C bond splitting in other catalytic processes.

In silico screening and biological evaluation of inhibitors of Src-SH3 domain interaction with a proline-rich ligand.

Src signalling and transduction are directly involved in cell growth, cell cycle, malignant transformation and cell migration, providing therapeutic opportunities through inhibition of Src. Here we report virtual screening for novel compounds that inhibit the Src-SH3 protein-protein interaction with a proline-rich peptide ligand. Computational docking of the ZINC compound database was performed using GOLD. Top-scoring compounds were assayed using a fluorescence polarization-based assay. A benzoquinoline derivative showed micromolar inhibition of binding between Src-SH3 and the proline-rich peptide. Several analogues were subsequently assayed showing the requirement of a linker between the benzoquinoline and phenyl rings, and electron donating substituents on the phenyl ring.

Computer-assisted single- or double-cut oblique osteotomies for the correction of lower limb deformities.

Corrective osteotomy interventions on lower extremities are widely accepted procedures for restoring axial alignment of lower limbs. However, some studies reveal failure rates of up to 70 per cent in a 10 year time frame, which indicates that the success of corrective osteotomies depends on multiple factors. Based on a comprehensive review of error sources among conventional correction osteotomy interventions, a novel approach was developed in order to reduce these error sources among all clinical working steps (deformity determination, planning, and intra-operative realization). The article describes the implemented methodology for realizing optimal correction osteotomies based on a six-dimensional or 12-dimensional optimization module for single- and double-cut oblique osteotomies. The results show that the realized planning and navigation concept enables reduction in the error sources among the clinical working steps of correction osteotomy interventions.

Coumarin-based inhibitors of human NAD(P)H:quinone oxidoreductase-1. Identification, structure-activity, off-target effects and in vitro human pancreatic cancer toxicity.

The enzyme human NAD(P)H quinone oxidoreductase-1 (NQO1), which is overexpressed in several types of tumor cell, is considered a design target for cancer therapeutics. We identify new coumarin-based competitive inhibitors of NQO1, one of which is nanomolar. Using computational docking and molecular dynamics, we obtain insights into the structural basis of inhibition. Selected inhibitors were then assessed for off-target effects associated with dicoumarol and were found to have differing effects on superoxide formation and mitochondrial respiration. A comparison of NQO1 inhibition and off-target effects for dicoumarol and its derivatives suggests that the ability of dicoumarol to kill cancer cells is independent of NQO1 inhibition, that cellular superoxide production by dicoumarol does not seem linked to NQO1 inhibition but may be related to mitochondrial decoupling, and that superoxide does not appear to be a major determinant of cytotoxicity. Implications are discussed for NQO1 inhibition as an anticancer drug design target and superoxide generation as the dicoumarol-mediated mechanism of cytotoxicity.

Nanoscale disorder in CaCu3Ti4O12: a new route to the enhanced dielectric response.

Significant nanoscale disorder of Cu and Ca atomic substitution is observed in CaCu(3)Ti(4)O(12), based on our integrated study using quantitative electron diffraction and extended x-ray absorption fine structure. Unambiguous identification of this previously omitted disorder is made possible by the unique sensitivity of these probes to valence-electron distribution and short-range order. Furthermore, first-principles-based theoretical analysis indicates that the Ca-site Cu atoms possess partially filled degenerate e(g) states, suggesting significant boost of dielectric response from additional low-energy electronic contributions. Our study points to a new route of enhancing dielectric response in transitional metal oxides by exploiting the strong electronic correlation beyond classical static pictures.

Application of glancing-emergent-angle fluorescence for polarized XAFS studies of single crystals.

X-ray absorption fine-structure (XAFS) data were obtained for the V K-edge for a series of anisotropic single crystals of (Cr(x)V(1-x))(2)O(3). The data and the results were compared for the as-prepared bulk single crystals (measured in fluorescence in two different orientations) and those ground to powder (measured in transmission). For the bulk single crystals, the glancing-emergent-angle (GEA) method was used to minimize fluorescence distortion. The reliability of the GEA technique was tested by comparing the polarization-weighted single-crystal XAFS data with the experimental powder data. These data were found to be in excellent agreement throughout the entire energy range. Thus, it was possible to reliably measure individual V-V contributions parallel and perpendicular to the c axis of the single crystals, i.e. those unavailable by powder data XAFS analysis. These experiments demonstrate that GEA is a premiere method for non-destructive high-photon-count in situ studies of local structure in bulk single crystals.