Large bronchial artery-pulmonary artery fistula due to cavitating tuberculosis.

Bronchial artery-pulmonary artery fistulae are rare vascular malformations most commonly caused by infection. Our case presents a 57-year-old male who presented to the Emergency Department with a symptomatic bronchial artery-pulmonary artery fistula due to cavitating pulmonary tuberculosis (TB). The diagnosis was made with multiphase CT angiography of the thorax (including pulmonary and systemic arterial phases). The patient was brought to interventional radiology for further investigation and management. The left upper lobe bronchial artery-pulmonary artery fistula was successfully identified and treated with endovascular embolization. Bronchial artery-pulmonary artery fistulae can pose a diagnostic and therapeutic challenge. Our case demonstrates endovascular embolization as an effective method of treating symptomatic bronchial artery-pulmonary artery fistulae.

Investigation of the structure of protein-polymer conjugates in solution reveals the impact of protein deuteration and the size of the polymer on its thermal stability.

The conjugation of proteins with polymers offers immense biotechnological potential by creating novel macromolecules. This article presents experimental findings on the structural properties of maltose-binding protein (MBP) conjugated with linear biodegradable polyphosphoester polymers with different molecular weights. We studied isotopic effects on both proteins and polymers. Circular dichroism and fluorescence spectroscopy and small-angle neutron scattering reveal that the conjugation process destabilizes the protein, affecting the secondary more than the tertiary structure, even at room temperature, and that the presence of two domains in the MBP may contribute to its observed instability. Notably, unfolding temperatures differ between native MBP and the conjugates. In particular, this study sheds light on the complex interplay of factors such as the deuteration influencing protein stability and conformational changes in the conjugation processes. The perdeuteration influences the hydrogen bond network and hydrophobic interactions in the case of the MBP protein. The perdeuteration of the protein influences the hydrogen bond network and hydrophobic interactions. This is evident in the decreased thermal stability of deuterated MBP protein, in the conjugate, especially with high-molecular-mass polymers.

Functional in vitro diversity of an intrinsically disordered plant protein during freeze-thawing is encoded by its structural plasticity.

Intrinsically disordered late embryogenesis abundant (LEA) proteins play a central role in the tolerance of plants and other organisms to dehydration brought upon, for example, by freezing temperatures, high salt concentration, drought or desiccation, and many LEA proteins have been found to stabilize dehydration-sensitive cellular structures. Their conformational ensembles are highly sensitive to the environment, allowing them to undergo conformational changes and adopt ordered secondary and quaternary structures and to participate in formation of membraneless organelles. In an interdisciplinary approach, we discovered how the functional diversity of the Arabidopsis thaliana LEA protein COR15A found in vitro is encoded in its structural repertoire, with the stabilization of membranes being achieved at the level of secondary structure and the stabilization of enzymes accomplished by the formation of oligomeric complexes. We provide molecular details on intra- and inter-monomeric helix-helix interactions, demonstrate how oligomerization is driven by an α-helical molecular recognition feature (α-MoRF) and provide a rationale that the formation of noncanonical, loosely packed, right-handed coiled-coils might be a recurring theme for homo- and hetero-oligomerization of LEA proteins.

Molecular interactions with bilayer membrane stacks using neutron and X-ray diffraction.

Lamellar unit cell reconstruction from neutron and X-ray diffraction data provides information about the disposition and position of molecules and molecular segments with respect to the bilayer. When supplemented with the judicious use of molecular deuteration, the technique probes the molecular interactions and conformations within the bilayer membrane and the water layer which constitute the crystallographic unit cell. The perspective is model independent, and potentially, with a higher degree of resolution than is available with other techniques. In the case of neutron diffraction the measurement consists of carefully normalised diffracted intensity under conditions of contrast variation of the water layer. The subsequent Fourier reconstruction of the unit cell is made using the phase information from variation of peak intensities with contrast. Although the phase problem is not as easily solved for the corresponding X-ray measurements, an intuitive approach can often suffice. Here we discuss the two complimentary techniques as probes of scattering length density profiles of a bilayer, and how such a perspective provides information about the location and orientation of molecules within or between lipid bilayers. Within the basic paradigm of lamellar phases this method has provided, for example, detailed insights into the location and interaction of cryoprotectants and stress proteins, of the mechanisms of actions of viral proteins, antimicrobial compounds and drugs, and the underlying structure of the stratum corneum. In this paper we review these techniques and provide examples of the systems that have been examined. We finish with a future outlook on the use of these techniques to improve our understanding of the interactions of membranes with biomolecules.

Shear influence on colloidal cluster growth: a SANS and USANS study.

This study examines the time evolution of silica/water clusters where the formation of a gel network from unitary silica particles is interrupted by a simple Couette shear field. The aim is to enable the general understanding of this simple system by examining the microscopic basis for the changes in viscosity by providing structural inputs from small-angle scattering for a simple theoretical model. The experimental system is an 8.3 nm particle silica solution (Ludox) where the gelation has been initiated by lowering the pH in a Couette cell providing a constant shear rate of 250 s-1. A unified small-angle neutron scattering (SANS) and ultra-small-angle neutron scattering (USANS) procedure is described to measure the scattered intensity in a wavevector range of 3 × 10-4 ≤ q (nm-1) ≤ 3.1 × 10-1, probing structural changes over a broad range of length scales from the nanometre to the micrometre. Scattering data provide a new means of better understanding the behaviour of colloidal clusters when subjected to an external applied shear over a continuous time sequence after gel initiation; a fit of the time-dependent scattered intensity leads to an estimation of the cluster's effective volume fraction and size as a function of time. A reductionist theoretical basis is described to predict the time-dependent viscosity behaviour of the sheared colloidal suspension gel-initiated cluster growth from the volume fraction of the clusters.

Double V-Y Island Pedicle Flap for Dorsal Hand Reconstruction Following Mohs Micrographic Surgery.

Medium to large defects on the dorsal hand pose a reconstructive challenge following dermatologic surgery. Repairs in this location can be complicated by a paucity of adjacent tissue reservoirs, competing tension vectors, thin cutaneous tissue, and superficial tendons and vasculature. In such cases, a double V-Y island pedicle flap is an effective reconstructive solution. It preserves hand function, harnesses local tissue with a robust blood supply, facilitates complete closure, and provides skin that closely matches the original's color and texture. Here, we present the repair of a medium to large dorsal hand defect after Mohs micrographic surgery for melanoma in situ, using a double V-Y island pedicle flap.

Bilateral Transposition Flaps With Split-Thickness Skin Grafting of Secondary Defects After a Large Mohs Micrographic Surgery Defect With Exposed Calvarium.

Large, full-thickness defects of the scalp create a common reconstructive dilemma following Mohs micrographic surgery. In cases with exposed calvarium, transposition flap(s) followed by split-thickness skin graft(s) to the secondary defect is an effective method of reconstruction that allows for same-day repair, full defect coverage, and good functional outcomes. Herein, we present the reconstruction of a large scalp defect utilizing bilateral transposition flaps followed by split-thickness skin grafts of the secondary defects.

Haemorrhagic cholecystitis treated with endovascular embolization.

Haemorrhagic cholecystitis is a rare complication of acute cholecystitis. Traditionally, treatment has been with emergency cholecystectomy. Endovascular management of haemorrhage allows the patient to be optimized for surgery at a later date. Our case presents a 52-year-old woman with haemorrhagic cholecystitis who underwent endovascular coil embolization of the cystic artery in interventional radiology. Further complications later ensued including a haematoma in the gallbladder fossa and a bile leak into the peritoneal cavity. As a result, the patient had an endoscopic retrograde cholangiopancreatography (ERCP) with placement of a covered stent into the extrahepatic bile ducts. The patient later developed abscess formation in the gallbladder fossa, which was managed with a percutaneous pigtail drain. Following clinical and radiological improvement, the patient was discharged with the gallbladder fossa drain and biliary stent in situ to await elective cholecystectomy. Endovascular embolization is a useful alternative, in the acute setting, to emergency surgical cholecystectomy.

Margination of 2D Platelet Microparticles in Blood.

Margination describes the movement of particles toward the endothelial wall within blood vessels. While there have been several studies tracking the margination of spherical particles in blood, the behavior of anisotropic particle shapes is not well described. In this study 2D platelet particles which possess many attractive qualities for use as a drug delivery system, with their high surface area allowing for increased surface binding activity, were directly monitored and margination quantified. The margination propensity of 1 and 2 µm 2D platelet particles was contrasted to that of 2 µm spherical particles at apparent wall shear rates (WSRs) of 50, 100, and 200 s-1 by both directly tracking labeled particles using fluorescent microscopy as well as using small-angle X-ray scattering (SAXS). For fluorescence studies, margination was quantified using the margination parameter M, which describes the number of particles found closest to the walls of a microfluidic device, with an M-value of 0.2 indicating no margination. Increased margination was seen in 2D platelet particles when compared to spherical particles tested at all flow rates, with M-values of 0.39 and 0.31 seen for 1 and 2 µm 2D platelet particles, respectively, while 2 µm spherical particles had an M-value of 0.21. Similarly, margination was observed qualitatively using SAXS, with increased scattering seen for platelet particles near the microfluidic channel wall. For all particles, increased margination was seen at increasing shear rates.

Phase separation in a ternary DPPC/DOPC/POPC system with reducing hydration.

The maintenance of plasma membrane structure is vital for the viability of cells. Disruption of this structure can lead to cell death. One important example is the macroscopic phase separation observed during dehydration associated with desiccation and freezing, often leading to loss of permeability and cell death. It has previously been shown that the hybrid lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) can act as a line-active component in ternary lipid systems, inhibiting macroscopic phase separation and stabilising membrane microdomains in lipid vesicles [1]. The domain size is found to decrease with increasing POPC concentration until complete mixing is observed. However, no such studies have been carried out at reduced hydration. To examine if this phase separation is unique to vesicles in excess water, we have conducted studies on several binary and ternary model membrane systems at both reduced hydration ("powder" type samples and oriented membrane stacks) and in excess water (supported lipid bilayers) at 0.2 mol fraction POPC, in the range where microdomain stabilisation is reported. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) are used to map phase transition temperatures, with X-ray and neutron scattering providing details of the changes in lipid packing and phase information within these boundaries. Atomic force microscopy (AFM) is used to image bilayers on a substrate in excess water. In all cases, macroscopic phase separation was observed rather than microdomain formation at this molar ratio. Thus POPC does not stabilise microdomains under these conditions, regardless of the type of model membrane, hydration or temperature. Thus we conclude that the driving force for separation under these conditions overcomes any linactant effects of the hybrid lipid.

Structural Characterization of Nanoparticle-Supported Lipid Bilayer Arrays by Grazing Incidence X-ray and Neutron Scattering.

Arrays of nanoparticle-supported lipid bilayers (nanoSLB) are lipid-coated nanopatterned interfaces that provide a platform to study curved model biological membranes using surface-sensitive techniques. We combined scattering techniques with direct imaging, to gain access to sub-nanometer scale structural information on stable nanoparticle monolayers assembled on silicon crystals in a noncovalent manner using a Langmuir-Schaefer deposition. The structure of supported lipid bilayers formed on the nanoparticle arrays via vesicle fusion was investigated using a combination of grazing incidence X-ray and neutron scattering techniques complemented by fluorescence microscopy imaging. Ordered nanoparticle assemblies were shown to be suitable and stable substrates for the formation of curved and fluid lipid bilayers that retained lateral mobility, as shown by fluorescence recovery after photobleaching and quartz crystal microbalance measurements. Neutron reflectometry revealed the formation of high-coverage lipid bilayers around the spherical particles together with a flat lipid bilayer on the substrate below the nanoparticles. The presence of coexisting flat and curved supported lipid bilayers on the same substrate, combined with the sub-nanometer accuracy and isotopic sensitivity of grazing incidence neutron scattering, provides a promising novel approach to investigate curvature-dependent membrane phenomena on supported lipid bilayers.

The flow of anisotropic nanoparticles in solution and in blood.

The alignment of anisotropic nanoparticles in flow has been used for a range of applications such as the preparation of strong fibres and the assembly of in-plane aligned 1D-nanoobjects that are used for electronic devices, sensors, energy and biological application. Important is also the flow behaviour of nanoparticles that were designed for nanomedical applications such as drug delivery. It is widely observed that non-spherical nanoparticles have longer circulation times and a more favourable biodistribution. To be able to understand this behaviour, researchers have turned to analyzing the flow of non-spherical nanoparticles in the blood stream. In this review, an overview of microfluidic techniques that are used to monitor the alignment of anisotropic nanoparticles in solution will be provided, which includes analysis by small angle X-ray scattering (SAXS) and polarized light microscopy. The flow of these nanoparticles in blood is then discussed as the presence of red blood cells causes margination of some nanoparticles. Using fluorescence microscopy, the extent of margination can be identified, which coincides with the ability of nanoparticles to adhere to the cells grown along the wall. While these studies are mainly carried out in vitro using blood, initial investigations in vivo were able to confirm the unusual flow of anisotropic nanoparticles.

Structural insights into self-assembly of a slow-evolving and mechanically robust supramolecular gel via time-resolved small-angle neutron scattering.

The supramolecular assembly process is a widespread phenomenon found in both synthetically engineered and naturally occurring systems, such as colloids, liquid crystals and micelles. However, a basic understanding of the evolution of self-assembly processes over time remains elusive, primarily owing to the fast kinetics involved in these processes and the complex nature of the various non-covalent interactions operating simultaneously. With the help of a slow-evolving supramolecular gel derived from a urea-based gelator, we aim to capture the different stages of the self-assembly process commencing from nucleation. In particular, we are able to study the self-assembly in real time using time-resolved small-angle neutron scattering (SANS) at length scales ranging from approximately 30 Å to 250 Å. Systems with and without sonication are compared simultaneously, to follow the different kinetic paths involved in these two cases. Time-dependent NMR, morphological and rheological studies act complementarily to the SANS data at sub-micron and bulk length scales. A hollow columnar formation comprising of gelator monomers arranged radially along the long axis of the fiber and solvent in the core is detected at the very early stage of the self-assembly process. While sonication promotes uniform growth of fibers and fiber entanglement, the absence of such a stimulus helps extensive bundle formation at a later stage and at the microscopic domain, making the gel system mechanically robust. The results of the present work provide a thorough understanding of the self-assembly process and reveal a path for fine-tuning such growth processes for applications such as the cosmetics industry, 3D printing ink development and paint industry.

Early percutaneous antegrade-retrograde rendezvous repair of a transected ureter-a real therapeutic option.

A 46-year-old female underwent elective laparoscopic hysterectomy. Seven days post-operatively, she presented with urinary leak from the vagina. Computed tomography urogram demonstrated a right complete ureteric transection with leakage of urine into the pelvis and fistulation into the vagina. A rendezvous procedure was performed via a retrograde cystoscopic approach during which a guidewire was used to cannulate the right ureteric orifice and coiled in the retroperitoneal cavity. Subsequently, via a right percutaneous nephrostomy, a guidewire was advanced through the site of ureteric transection, which was followed by a snare catheter to bring the retrograde wire externally. A nephroureteric stent was then inserted. Twelve weeks later, the nephroureteric stent was exchanged for a ureteric stent for 6 months. A subsequent retrograde ureterogram showed complete healing of the ureter. The ureteric stent was removed and follow-up ultrasounds revealed no hydronephrosis. Percutaneous rendezvous procedures represent an effective option to treat this challenging condition.

Controlling phase and rheological behaviours of hexagonal lyotropic liquid crystalline templates for nanostructural administration and retention.

Introducing polymerizable monomers into a binary hexagonal lyotropic liquid crystalline (LLC) template is a straightforward way for retaining the nanostructure but will decrease attractive intra- and inter- aggregate interactions. It is therefore crucial to understand the interfacial interactions at nanoscale after introducing the monomers but prior to polymerization. Herein, active species, poly (ethylene glycol) diacrylate (PEGDA) and 2-hydroxyethyl methacrylate (HEMA), were introduced into hexagonal LLC of dodecyl trimethylammonium bromide and water to explore the structural variables, dimensional stability, and dynamic property. At a proper volume ratio of PEGDA/HEMA (1/4), the system presents excellent homogeneity with a higher dimensional stability and lower dynamic property from rheological assessments, thereby achieving robust, free-standing, and transparent membranes after photo-polymerization. The unique property of the system also lies in the much lower order-disorder transition temperature (45 °C) that facilitates the reorientation of mesochannels. They are in contrast inaccessible for the ternary system only with PEGDA, though the nanostructure for both systems could be retained. An insight into subtle variations in these parameters allows us to prepare a polymerizable template possessing higher dimensional stability and suitable flexibility via molecular design, thereby enabling simultaneous structural alignment and retention for the development of functional nanomaterials.

Hybrid Nanoparticles for Haloperidol Encapsulation: Quid Est Optimum?

The choice of drug delivery carrier is of paramount importance for the fate of a drug in a human body. In this study, we have prepared the hybrid nanoparticles composed of FDA-approved Eudragit L100-55 copolymer and polymeric surfactant Brij98 to load haloperidol-an antipsychotic hydrophobic drug used to treat schizophrenia and many other disorders. This platform shows good drug-loading efficiency and stability in comparison to the widely applied platforms of mesoporous silica (MSN) and a metal-organic framework (MOF). ZIF8, a biocompatible MOF, failed to encapsulate haloperidol, whereas MSN only showed limited encapsulation ability. Isothermal titration calorimetry showed that haloperidol has low binding with the surface of ZIF8 and MSN in comparison to Eudragit L100-55/Brij98, thus elucidating the striking difference in haloperidol loading. With further optimization, the haloperidol loading efficiency could reach up to 40% in the hybrid Eudragit L100-55/Brij98 nanoparticles with high stability over several months. Differential scanning calorimetry studies indicate that the encapsulated haloperidol stays in an amorphous state inside the Eudragit L100-55/Brij98 nanoparticles. Using a catalepsy and open field animal tests, we proved the prolongation of haloperidol release in vivo, resulting in later onset of action compared to the free drug.

C-amidation of substitutedß3oligoamides yields novel supramolecular assembly motif.

N-acylated substitutedß3oligoamides are known to form unique supramolecular nanorods based on a 3-point hydrogen bond self-assembly motif. This motif is an intermolecular extension of the hydrogen bonding network that stabilizes the 14-helix secondary structure unique toß3oligoamides. Acetylation of the N-terminus of the molecule provides the necessary third hydrogen bond pair of the motif. Here, the possibility of introducing the third hydrogen bond pair via amidation of the C terminus is investigated. While similar in purpose, this modification introduces a chemically distinct new self-assembly motif, also removing the bulky carboxyl group that does not fold into the 14 helix positioning instead as a side chain. Three substitutedß3oligoamide variants with the base sequence LIA (where the letters denoteß3residues with side chains analogous to α amino acids) were compared: N-acylated Ac-ß3[LIA] as a reference, C-amidatedß3[LIA]-CONH2, andß3[LIA] with free unmodified N and C termini as a negative control. The three variants were dissolved in water to promote self-assembly. The self-assembly was characterised using mid- and far-infrared spectroscopy, small angle x-ray scattering (SAXS) and atomic force microscopy (AFM). IR measurements confirmed that all three samples were in a similar conformation, consistent with pseudo 14-helical secondary structures. Far-infrared spectroscopy measurements ofß3[LIA]-CONH2showed distinct peaks consistent with highly organised skeletal modes, i.e. regular supramolecular assembly, that was largely absent from the other two oligoamides. Modelling of SAXS data is consistent with elliptical cylinder structures resulting from nanorod bundling for bothß3[LIA]-CONH2and Ac-ß3[LIA], but not in the unmodified sample. Consistently, AFM imaging showed large nanorod bundling structures inß3[LIA]-CONH2, varied bundling structures in Ac-ß3[LIA], and only aggregation inß3[LIA]. Amidation showed much more organised and robust assembly compared to acetylation, providing a new, easy to synthesize self-assembly motif for helical nanorod assembly that is similar but distinct to N-acylation.

Conformation of poly(ethylene glycol) in aqueous cholinium amino acid hybrid solvents.

HYPOTHESIS: Hybrid solvents based on cholinium amino acid ionic liquids ([Ch][AA] ILs) mixed with water are environmentally benign solvents with low toxicity. [Ch][AA] ILs are used in biomass pretreatment processes to dissolve targeted (macro)molecules such as lignin from lingnocellulose. Understanding how [Ch][AA] ILs dissolve polymers is therefore of great interest for the rational design of ILs towards industrial application. Variation of the IL anion and the water concentration are hypothesised to change the solvent properties of [Ch][AA] hybrid solvents. Therefore, we probe the solvent quality of [Ch][AA] aqueous solutions with different anions (glycinate, prolinate and argininate) and water concentration for the simple model solute poly(ethylene glycol) (PEG). EXPERIMENTS: Partial phase diagrams were produced to probe the salting-out effect of [Ch][AA] ILs towards PEG (Mw = 38 kDa). Small-angle neutron scattering experiments of deuterated PEG in hydrogenous [Ch][AA] aqueous solutions were performed to determine the polymer radius of gyration at infinite dilution (Rg,0) via Zimm-plots. Polymer concentration dependent apparent Rg values were obtained fitting an excluded volume polymer model onto the scattering data. Blends of hydrogenous and deuterated PEG under zero average contrast conditions were analysed to probe Rg at high polymer concentrations. FINDINGS: Hydrogen bond capacity of the anion is key to the salting-out effect of [Ch][AA] ILs on PEG. Rg,0 depends on anion species and water concentration. At IL:water = 1:30 (mole:mole) and 37 °C, cholinium argininate and cholinium glycinate are close to theta solvents while cholinium prolinate and dilute cholinium argininate (IL:water = 1:100) are between theta and good solvents.

The Protein Corona Leads to Deformation of Spherical Micelles.

The formation of a non-specific protein corona around nanoparticles (NPs) has been identified as one of the culprits for failed nanomedicine. The amount and type of adsorbed protein from the blood plasma are known to determine the fate of NPs and the accessibility of targeting ligands. Herein, we show that the adsorbed protein may not only enlarge the NPs and change their surface properties but also, in the case of soft NPs such as polymer micelles, lead to deformation. Poly(1-O-methacryloyl -ß-D-fructopyranose)-b-poly(methylmethacrylate) (P(1-O-MAFru)-b-PMMA) block co-polymers were self-assembled into NPs with a spherical core-shell morphology as determined by small angle neutron scattering (SANS). Upon incubation with albumin, TEM, SANS, and small angle X-ray scattering (SAXS) revealed the adsorption of albumin and deformation of the NPs with a spheroid geometry. Removal of the protein led to the reversal of the morphology back to the spherical core-shell structure. Structural studies and cell studies of uptake of the NPs imply that the observed deformation may influence blood circulation time and cell uptake.