Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Whey protein improves the stability of C-phycocyanin in acidified conditions during light storage.

C-phycocyanin is a bright blue natural colorant used in food and beverage applications. However, its color stability is poor in acidic conditions under exposure to light. In this work, we study the use of whey protein isolate (WPI) to protect C-phycocyanin from color degradation. Low concentration (0.05-0.1%) WPI addition delayed (~2 days) the color degradation of C-phycocyanin at pH 3.0 over 5-day storage in light. However, the color degradation was aggravated adversely during 5-day light storage when C-phycocyanin mixed with a higher concentration (~1%) of WPI degraded after heat-treatment. The Fourier transform infrared and fluorescence spectroscopy confirmed that structural changes (e.g., alpha-helix protection and transformation from alpha-helix to beta-sheet) of C-phycocyanin due to interaction with WPI. These results, along with quartz crystal microbalance with dissipation technology outcomes, suggest that a low concentration of WPI may help protect C-phycocyanin's secondary structure from becoming damaged during light storage, preventing its color degradation.

Investigation of the Interaction between N-Acetyl-l-Cysteine and Ovalbumin by Spectroscopic Studies, Molecular Docking Simulation, and Real-Time Quartz Crystal Microbalance with Dissipation.

This study investigated the interaction between N-acetyl-l-cysteine (NAC) and ovalbumin (OVA) using multispectroscopic technology, molecular docking, and quartz crystal microbalance with dissipation (QCM-D). Fluorescence intensity and UV absorption of OVA were decreased substantially upon the addition of NAC. The calculated Kq values were obtained at 298, 304, and 310 K for 13.48, 15.59, and 17.50 (× 1012 L mol-1), respectively, suggesting that the static quenching was dominated. Thermodynamic parameters such as ΔH (-150.58 kJ mol-1), ΔS (-433.51 J mol-1 K-1), and ΔG values (-21.39 kJ mol-1), combined with molecular docking and QCM-D data, showed that the interaction was spontaneous and van der Waals and hydrogen bonding were identified as the main driving forces. FTIR and CD results showed that the α-helix content of OVA increased from 2.8 to 22.9%, and the ß-sheet decreased from 0.2 to 21.9% in the presence of 5 and 10 µM NAC, respectively, compared to the pure OVA, respectively.

Adsorption of polypropylene oxide-polyethylene oxide type surfactants at surfaces of pharmaceutical relevant materials: effect of surface energetics and surfactant structures.

Protein therapeutics are exposed to various surfaces during product development, where their adsorption possibly causes unfolding, denaturation, and aggregation. In this paper, we aim to characterize four types of typical surfaces used in the development of biologics: polycarbonate, polyethersulfone, borosilicate glass, and cellulose. Contact angles of these surfaces were measured using three probing liquids: water, formamide, and diidomethane, from which acid/base (AB) and Lifshitz-van der Waals (LW) interaction components were derived. To explore the interactions of surfactants of Pluronics/Poloxamers (PEO-PPO-PEO copolymers) with these surfaces, the adsorption of three Pluronics (F68, F127, and L44) at these surfaces was determined using a quartz crystal microbalance with dissipation technique (QCM-D). For hydrophobic surfaces without AB component (polycarbonate and polyethersulfone), these copolymers exhibited significant adsorption with a little dissipation at low concentrations. For hydrophilic surfaces with AB component (cellulose and borosilicate), the adsorption at low-surfactant concentration is low while dissipation is relatively high. Additionally, the chemical properties of Pluronics such as the ratio of PPO to PEO, along with the interaction of PPO with surfaces were observed to play a critical role in adsorption. Furthermore, the interfacial structure of the adsorbed layer was affected by both AB interaction and the presence of PEO block.

Engineering fast dissolving sodium acetate mediated crystalline solid dispersion of docetaxel.

It is hypothesized that a novel crystalline solid dispersion (CSD) of docetaxel (C-DXT) can be engineered by dispersing native docetaxel (DXT, a BCS class II drug) in sodium acetate crystal (SA). DXT is dissolved in glacial acetic/SA solution and freeze-dried. The resulting C-DXT is characterized by differential scanning calorimetry (DSC), powder X-ray analysis (PXRD), LC-MS/MS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Quartz crystal microbalance with dissipation monitoring (QCM-D) and dynamic light scattering (DLS). Its cytotoxicity on model cancerous (MCF-7, MDA-MB-468) and normal breast cells (MCF-10A) is assessed by MTS assay. SEM/TEM data and the absence of the characteristics peaks of DXT on the DSC curve (at 193.4 °C) and the XRD scan (at 2θ = 15.31 °C and 23.04 °C) confirm the presence of C-DXT in SA. The LC-MS/MS data indicates the chemical stability of DXT. The yield and C-DXT loading are 95.2% and 6.52% w/w, respectively. The C-DXT rapidly forms an aqueous non-rigid nanosuspension with a faster drug dissolution rate compared to native DXT. Unlike, control Tween 80/ethanol, SA is noncytotoxic to normal cells. However, C-DXT's cytotoxicity is time and dose dependent for all diseased cells. This unique CSD process might be applicable to other hydrophobic bioactive agents to enhance their safety and efficacy.

Developing a core outcome set for chronic rhinosinusitis: a systematic review of outcomes utilised in the current literature.

BACKGROUND: A core outcome set (COS) is an agreed standardised collection of outcomes that should be measured and reported by all trials for a specific clinical area, in this case chronic rhinosinusitis. These are not restrictive and researchers may continue to explore other outcomes alongside these that they feel are relevant to their intervention. The aim of this systematic review was to identify the need for a COS for chronic rhinosinusitis. METHODS: A sensitive search strategy was used to identify all published Cochrane systematic reviews and randomised control trials of intervention for adult patients with chronic rhinosinusitis. Two independent authors reviewed these to obtain a list of outcomes and outcome measures reported by each clinical trial. RESULTS: Sixty-nine randomised control trials and eight Cochrane systematic reviews were included in this study. They reported 68 individual outcomes and outcome measures, with an average of four to ten outcomes per clinical trial. These outcomes were mapped to 23 subcategories belonging to eight core categories. CONCLUSIONS: The key finding of this review was the heterogeneity of outcomes reported and measured by clinical trials of patients with chronic rhinosinusitis, precluding meaningful meta-analysis of data. This review supports the need for development of a COS, to be used in future trials on adult patients with chronic rhinosinusitis.

Hypernatremia in the Neonate: Neonatal Hypernatremia and Hypernatremic Dehydration in Neonates Receiving Exclusive Breastfeeding.

AIMS AND OBJECTIVES: Evaluation of neonatal hypernatremia and hypernatremic dehydration in neonates receiving exclusive breastfeeding. INTRODUCTION: Neonatal hypernatremia is a serious condition in the newborn period. We present infants with hypernatremic dehydration due to breast milk (BM) hypernatremia. Hypernatremic dehydration in breast-fed newborns is usually secondary to insufficient lactation. We present the neonatal hypernatremia and hypernatremic dehydration encountered between January and December, 2012, its causes and treatment. METHODOLOGY: This was a retrospective study. We analyzed records of babies admitted to the Neonatal Intensive Care Unit who were investigated and found to have hypernatremia and whose mother's BM sodium (BM Na) was done. INCLUSION CRITERIA: (1) Babies with serum Na >145 meq/l, (2) euglycemia, (3) normocalcemic, (4) no clinical and lab evidence of sepsis, (5) exclusive breast feeds. EXCLUSION CRITERIA: Neonates not satisfying any mentioned criterion. RESULTS: BM Na correlated strongly with neonatal hypernatremia in exclusively breast-fed babies who did not otherwise have any risk factor. CONCLUSION: Elevated BM Na is an important etiological factor in neonatal hypernatremia.

Particle Characterization for a Protein Drug Product Stored in Pre-Filled Syringes Using Micro-Flow Imaging, Archimedes, and Quartz Crystal Microbalance with Dissipation.

Micro-flow imaging (MFI) has been used for formulation development for analyzing sub-visible particles. Archimedes, a novel technique for analyzing sub-micron particles, has been considered as an orthogonal method to currently existing techniques. This study utilized these two techniques to investigate the effectiveness of polysorbate (PS-80) in mitigating the particle formation of a therapeutic protein formulation stored in silicone oil-coated pre-filled syringes. The results indicated that PS-80 prevented the formation of both protein and silicone oil particles. In the case of protein particles, PS-80 might involve in the interactions with the hydrophobic patches of protein, air bubbles, and the stressed surfaces of silicone oil-coated pre-filled syringes. Such interactions played a role in mitigating the formation of protein particles. Subsequently, quartz crystal microbalance with dissipation (QCM-D) was utilized to characterize the interactions associated with silicone oil, protein, and PS-80 in the solutions. Based on QCM-D results, we proposed that PS-80 likely formed a layer on the interior surfaces of syringes. As a result, the adsorbed PS-80 might block the leakage of silicone oil from the surfaces to solution so that the silicone oil particles were mitigated at the presence of PS-80. Overall, this study demonstrated the necessary of utilizing these three techniques cooperatively in order to better understand the interfacial role of PS-80 in mitigating the formation of protein and silicone oil particles.

Mechanistic understanding of protein-silicone oil interactions.

PURPOSE: To investigate interactions between protein and silicone oil so that we can provide some mechanistic understanding of protein aggregation in silicone oil lubricated syringes and its prevention by formulation additives such as Polysorbate 80 and Poloxamer 188. METHODS: Interfacial tension values of silicone oil/water interface of abatacept solutions with and without formulation additives were obtained under equilibrium conditions using Attension Theta optical tensiometer. Their adsorption and desorption profiles were measured using Quartz Crystal Microbalancing with Dissipation monitoring (QCM-D). The degree of aggregation of abatacept was assessed based on size exclusion measurement. RESULTS: Adsorption of abatacept at the oil/water interface was shown. Polysorbat 80 was more effective than Poloxamer 188 in preventing abatacept adsorption. Moreover, it was noted that some of the adsorbed abatacept molecules were not desorbed readily upon buffer rinse. Finally, no homogeneous aggregation was observed at room temperature and a slight increase of aggregation was only observed for samples measured at 40°C which can be prevented using Polysorbate 80. CONCLUSIONS: Interfacial adsorption of proteins is the key step and maybe responsible for the phenomenon of soluble-protein loss when contacting silicone oil and the irreversible adsorption of protein may be associated with protein denaturation/aggregation.

Mechanism of the cooperative adsorption of oppositely charged nanoparticles.

Quartz crystal microbalance experiments were performed to study the kinetics of surface adsorption from solutions containing oppositely charged nanoparticles. A theoretical model was developed according to which formation of dense nanoparticle (NP) monolayers is driven by a cooperative process, in which the already-adsorbed NPs facilitate adsorption of NPs from solution. The kinetic rate constants change with the NP solution concentration and can be used to backtrack adsorption free energies. These energies agree with the predictions of a simple DLVO model.

Unimolecular rectification of monolayers of CH3C(O)S-C14H28Q(+)-3CNQ(-) and CH3C(O)S-C16H32Q(+)-3CNQ(-) organized by self-assembly, Langmuir-Blodgett, and Langmuir-Schaefer techniques.

The advantage of "self-assembly" (strong covalent binding to substrates) was combined with the advantage of Langmuir-Blodgett (LB) or Langmuir-Schaefer (LS) transfer to a solid substrate (quantitative transfer of monolayers to the substrate). The electrical rectification (asymmetric conduction) by a monolayer of thioacetylalkylquinolinium tricyanoquinodimethanide was critically compared when these molecules had been transferred, by such competing techniques, onto gold electrodes, and then covered by a "cold gold" pad electrode. Unimolecular rectification was observed in the expected directions in the LB and LS monolayers. The Self-Assembled Monolayers (SAMs) were disordered; macroscopic measurements of rectification were unsuccessful for the SAMs, but successful for the down-stroke LB and LS monolayers, whose orientation and potential bonding to the Au surface should be identical to that of an ideal SAM.

Spectroscopy and rectification of three donor-sigma-acceptor compounds, consisting of a one-electron donor (pyrene or ferrocene), a one-electron acceptor (perylenebisimide), and a C19 swallowtail.

We report spectroscopic characterization and unimolecular rectification (asymmetric electrical conduction) measurements of three donor-sigma-acceptor (D-sigma-A) compounds N-(10-nonadecyl)-N-(1-pyrenylmethyl)perylene-3,4,9,10-bis(dicarboximide) (1), N-(10-nonadecyl)-N-(4-[1-pyrenyl]butyl)perylene-3,4,9,10-bis(dicarboximide) (2), and N-(10-nonadecyl)-N-(2-ferrocenylethyl)perylene-3,4,9,10-bis(dicarboximide) (3). These molecules were arranged as one-molecule thick Langmuir-Blodgett monolayers between Au electrodes. In such an "Au | D-sigma-A | Au" sandwich, molecule 1 is a unimolecular rectifier, with rather small rectification ratios (between 2 and 3 at +/-1 V) that decrease upon cycling. Molecule 2 does not rectify. Molecule 3 rectifies, with a rectification ratio of between 14 and 28 at +/-1 V; the through-film rectification and currents persist, even with scans of +/-2 V, for up to 40 cycles of measurement. Qualitative arguments, based on a two-level rectification mechanism, are consistent with the current asymmetries observed in the monolayers of 1 and 3.

Coupled surface-enhanced Raman spectroscopy and electrical conductivity measurements of 1,4-phenylene diisocyanide in molecular electronic junctions.

Probing the structure of molecules in a metal-molecule-metal junction under an applied voltage is critical for understanding molecular electron transport properties. We present an approach that allows recording surface-enhanced Raman spectra simultaneously with electrical measurements of a monolayer of molecules in molecular electronic junctions. 1,4-Phenylene diisocyanide in two different types of junctions was used to illustrate the approach. The results show that the molecular integrity was intact in the molecular junctions and under the applied bias. The monolayer sensitivity of the approach provides a new powerful tool for characterizing molecular structure in a molecular electronic junction.

Current rectification in a Langmuir-Schaefer monolayer of fullerene-bis-[4-diphenylamino-4' '-(n-ethyl-n-2' ''-ethyl)amino-1,4-diphenyl-1,3-butadiene] malonate between Au electrodes.

Langmuir-Schaefer (LS) monolayer films of fullerene-bis-[4-diphenylamino-4' '-(N-ethyl-N-2' ''-ethyl)amino-1,4-diphenyl-1,3-butadiene] malonate, 1, sandwiched between two Au electrodes, exhibit pronounced current asymmetries (rectification) between positive and negative bias at room temperature, with no decay of the rectification after several cycles. The device shows symmetrical through-space tunneling for a bias up to +/-3 V, and asymmetrical, unimolecular, "U" type rectifier behavior in the voltage range from +/-3.0 to +/-5.4 V, with rectification ratios up to 16.5. The rectification is ascribed to the asymmetric placement of the relevant molecular orbitals, with respect to the metallic electrodes.