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Integration of advanced technologies have revitalised treatment methods in the current clinical practice. In orthopaedic surgery, patient-specific implants have leveraged the design freedom offered by additive manufacturing (AM) exploiting the capabilities within powder bed fusion processes. Furthermore, generative design (GD), a design exploration tool based on the artificial intelligence, can integrate manufacturing constraints in the concept development phase, consequently bridging the gap between AM design and manufacturing. However, the reproducibility of implant prototypes are severely constrained due to uncomprehensive information on manufacturing and post processing techniques in the detailed design phase. This paper explores the manufacturing feasibility of novel GD concept plate designs for High Tibial Osteotomy (HTO), a joint preserving surgery for a patient diagnosed with osteoarthritis in the knee. A design for AM (DfAM) workflow for a generatively designed HTO plate is presented, including; detailed DfAM of GD concept designs, fabrication of plate prototypes using electron beam powder bed fusion (PBF-EB) of medical grade Ti-6Al-4 V, post processing and inspection. The study established PBF-EB as a suitable manufacturing method for the highly complex GD plate fixations, through evaluating the impact of manufacturing and post processing on the surface finish and geometrical precision of the plate design features.

AbstractBouveret syndrome is the rarest variant of gallstone ileus, with a high morbidity and mortality rate as well as life-threatening complications. We present a case of an 86-year-old woman who presented with abdominal pain and was diagnosed with acute cholecystitis. After laparoscopic cholecystectomy, her symptoms did not improve. She then underwent endoscopic retrograde cholangiopancreatography and was found to have a stone causing duodenal bulb obstruction. The stone was removed using a snare, and her symptoms improved greatly. This rare case of Bouveret syndrome with no apparent fistula was successfully treated using endoscopic measures.

MolMod, a web-based database for classical force fields for molecular simulations of fluids [Mol. Sim. 45, 10 (2019), 806–814], was extended to transferable force fields. Eight transferable force fields, including all-atom and united-atom type force fields, were implemented in the MolModdatabase: OPLS-UA, OPLS-AA, COMPASS, CHARMM, GROMOS, TraPPE, Potoff, and TAMie. These transferable force fields cover a large variety of chemical substance classes. The system is designed such that new transferable force fields can be readily integrated. A graphical user interface was implemented that enables the construction of molecules. The MolModdatabase compiles the force field for the specified component and force field type and provides the corresponding data and meta data as well as ready-to-use input files for the molecule for different simulation engines. This helps the user to flexibly choose molecular models and integrate them swiftly in their individual workflows, reducing risks of input errors in molecular simulations.

C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether or how these proteins regulate transcription. Most of the ∼700 human C2H2-ZF proteins also contain at least one KRAB, SCAN, BTB, or SET domain, suggesting that they may have common interacting partners and/or effector functions. Here, we report a multifaceted functional analysis of 131 human C2H2-ZF proteins, encompassing DNA binding sites, interacting proteins, and transcriptional response to genetic perturbation. We confirm the expected diversity in DNA binding motifs and genomic binding sites, and provide motif models for 78 previously uncharacterized C2H2-ZF proteins, most of which are unique. Surprisingly, the diversity in protein–protein interactions is nearly as high as diversity in DNA binding motifs: Most C2H2-ZF proteins interact with a unique spectrum of co-activators and co-repressors. Thus, multiparameter diversification likely underlies the evolutionary success of this large class of human proteins.

We describe the safe use of a modified Allen® table to place two parturients in the prone position for surgery under general anaesthesia. Both patients were in the third trimester of pregnancy and presented with cauda equina syndrome requiring urgent surgical decompression. A modification of the Allen® spinal table allowed safe prone positioning with minimal maternal or fetal compromise whilst ensuring adequate surgical access to the lumbar spine. We have shown that patients in advanced pregnancy needing surgical intervention can be safely anaesthetised and positioned prone for their spinal surgery following careful planning and multidisciplinary teamwork.

AbstractMeckel’s diverticulum is a true diverticulum caused by the incomplete obliteration of the vitelline duct during gestation. It is the most common congenital malformation of the gastrointestinal tract. Meckel’s diverticulum is a rare presentation in adults, especially because symptomatic patients present in early childhood. We present a 57-year-old woman with symptomatic iron deficiency after recent nonsteroidal anti-inflammatory use. After normal upper and lower endoscopy, a capsule endoscopy showed an oozing polyp in the distal ileum. The small bowel was surgically resected, and histopathology confirmed Meckel’s diverticulum as the cause of her small bowel bleeding. Rare causes such as Meckel’s diverticulum should be kept in mind in the differential diagnosis for patients with suspected small bowel bleeding.

To determine the anatomic and visual outcomes of patients with ophthalmic artery segment aneurysms treated at The Johns Hopkins Hospital using a consensus-based treatment algorithm.

Details of a large scale modular 1-g laminar box system capable of simulating seismic induced liquefaction and lateral spreading response of level or gently sloping loose deposits of up to 6 m depth are presented. The internal dimensions of the largest module are 5 m in length and 2.75 m in width. The system includes a two dimensional laminar box made of 24 laminates stacked on top of each other supported by ball bearings, a base shaker resting on a strong floor, two computer controlled high speed actuators mounted on a strong wall, a dense array advanced instrumentation, and a novel system for laboratory hydraulic placement of loose sand deposit, which mimics underwater deposition in a narrow density range. The stacks of laminates slide on each other using a low-friction high-load capacity ball bearing system placed between each laminate. It could also be reconfigured into two smaller modules that are 2.5 m wide, 2.75 m long, and up to 3 m high. The maximum shear strain achievable in this system is 15 %. A limited set of instrumentation data is presented to highlight the capabilities of this equipment system. The reliability of the dense array sensor data is illustrated using cross comparison of accelerations and displacements measured by different types of sensors.

Background A variety of modalities are available for the control of recurrent epistaxis in hereditary hemorrhagic telangiectasia (HHT). Laser ablation, in particular potassium-titanyl-phosphate (KTP), has gained popularity as it coagulates the telangiectasia with minimal peripheral tissue injury. Septodermoplasty (SDP) also can be performed in the day surgery setting. Telangiectasia recurred, necessitating repeated treatments. The frequency and interval between procedures is not well documented. The purpose of this study was to describe the frequency of surgical interventions for HHT patients and the impact of SDP.Methods A retrospective review was undertaken of procedures performed in a tertiary hospital unit during a 60-month period for HHT. The incidence of KTP laser and SDP, days between treatments, total number of interventions and perioperative hemoglobin (Hb) were audited. Patient groups were identified as definite or possible HHT according to the Curacao criteria. All suffered from epistaxis sufficient to seek medical treatment.Results Three hundred one procedures were performed on 131 patients during the study period. In total, 33 SDPs and 268 KTP laser treatments were performed; 78.3% of patients required three or less procedures. The mean time interval between treatments was 473 (±515 days) days. The rate of KTP after an SDP decreased from 1.83 (±1.99) to 0.78 (±0.85; p = 0.012). Hb level was not associated with treatments required.Conclusion Surgical interventions with laser and SDP in HHT are always time limited as recurrence of telangiectasia is inevitable. This study discusses the expectations of therapy, mainly frequency and duration of effect, along with the impact of SDP. The outcomes assist in better management of patient expectations.

AbstractThrombotic complications such as venous thromboembolism, ischemic stroke, and myocardial infarction have emerged as causes of significant morbidity and mortality in patients infected with COVID-19. We present a 32-year-old man who developed a large saddle pulmonary embolus secondary to COVID-19 infection and underwent successful bilateral percutaneous pulmonary artery mechanical thrombectomy.

Objectives:To evaluate the medium‐term outcome of cricothyroid approximation and subluxation (CTAS) with postoperative speech therapy for pitch elevation in male‐to‐female transsexuals.

Objective:To validate the Child Health Questionnaire (CHQ) and assess the quality of life of inner‐city British children with adenotonsillar disease.

We describe a new technique for removing anterior vocal fold lesions, which cannot be visualized with conventional suspension laryngoscopy. These situations are rare and the only alternative surgeons have had previously is an open laryngeal procedure. The technique we describe involves the use of a laryngeal mask airway (LMA), a flexible bronchoscope with biopsy channel, a 400 μm laser fibre and KTP/532 nm laser. This method was used to treat two patients in whom conventional suspension laryngoscopy had previously been attempted and abandoned.

We present the results of a confidential telephone survey of ENT units in England on the disinfection of flexible fibre-optic nasendoscopes out-of-hours. The on-call residents of 124 units were contacted and questioned. In 35.1 per cent of units surveyed, the on-call resident was primarily responsible for cleaning the scopes after use. Only 46 per cent of these junior doctors had access to a chemical sterilant to allow for high-level disinfection of these scopes. Provision for disinfection of scopes was poorer in teaching hospitals and in units that served inner city populations. Only 12.1 per cent of Senior House Officers (SHOs) received any training in disinfection techniques and only 25.5 per cent of units kept a register of patients nasendoscoped out-of-hours for purposes of contact tracing.

The fluorescence decays of the pyrene monomer of a series of pyrene-labeled poly(N,N-dimethylacrylamide)s (PyPDMAAm) were acquired in N,N-dimethylformamide (DMF) and acetone with different concentrations of nitromethane and at very low polymer concentration. DMF and acetone are good and mediocre solvents for PyPDMAAm, respectively. Nitromethane is a potent quencher of pyrene. Nitromethane addition to the polymer solution shortens the pyrene lifetime. The fluorescence decays of the quenched and unquenched pyrene-labeled polymers were analyzed with a blob model. Shortening the lifetime of pyrene reduces the volume probed by the dye while it remains excited. For each quencher concentration, the blob volume and size were determined, and scaling laws were shown to hold. The exponents retrieved from the scaling relationships agreed with those reported in polymer science textbooks.

Pyrene-labeled poly(N,N-dimethylacrylamide)s were prepared by radical copolymerization of N,N-dimethylacrylamide with N-(1-pyrenylmethyl)acrylamide. The progress of the copolymerization reaction was followed by ¹H NMR to ensure that the pyrene-labeled monomer was homogeneously incorporated into the polymer backbone. Since pyrene is hydrophobic and poly(N,N-dimethylacrylamide) is water-soluble, a set of water-soluble associative polymers was generated. The effect of solvent quality toward these associative polymers was investigated. The level of association and the kinetics of encounter between pendants were determined in N,N-dimethylformamide (DMF), acetone, water, and mixtures of acetone and water. Analysis of the fluorescence decays with a blob model yields quantitative results which agree with the qualitative information retrieved by other techniques (static light scattering, intrinsic viscosity, UV−vis absorption). The level of association between hydrophobic pendants was found to be small in acetone (a good solvent for pyrene). It increases when water is added to the solution, since pyrene is insoluble in water. The level of association is smaller in DMF than in acetone, because DMF is a better solvent than acetone for the polymer, and swelling of the polymer coil results in a decrease of the interactions existing between the pyrene groups.

AbstractRhabdomyosarcoma of the adult head and neck is rare, particularly beyond 40 years of age. In this region, the nasopharynx is an unusual site. Most nasopharyngeal rhabdomyosarcomas are of an alveolar variety. We report a case of embryonal or spindle cell rhabdomyosarcoma in the nasopharynx of a 47-year-old man. The histology of this tumour revealed clear cells that have not been described in embryonal rhabdomyosarcomas occurring in the head and neck. The pathology is discussed and current literature reviewed.Copyright © 2002 S. Karger AG, Basel

Two polyethylene glycols (PEG, M = 35 000) end-capped with short fluorocarbon tails were synthesized and characterized. In aqueous solution, the fluorocarbon portions associate strongly to form micelle-like structures which are bridged by PEG chains to form a three-dimensional network. As a result, these polymers in solution exhibit unusual rheological properties as a function of fluorocarbon length, polymer concentration, and shear rate (frequency). Their zero-shear viscosity increases with concentration, a common behavior of associating polymers. The viscosity is dramatically enhanced by replacing the end hydrophobe C6F13 with C8F17, a consequence of the stronger association interaction of C8F17 in aqueous solution. The polymer with the longer end group exhibits strong shear thinning once a critical shear rate is reached, whereas for the C6F13 end-capped polymer, we cannot with our equipment reach the shear-thinning regime. Our data indicate that between 2 and 6 wt %, and perhaps over a wider range of concentrations, both systems can be characterized in terms of identical values of the plateau modulus GN°, implying a similar concentration of chains bridging micelles in each system. The GN° values increase strongly with polymer concentration, consistent with a larger fraction of bridging chains and a smaller fraction of looping chains at elevated concentration. The viscosity difference between the two polymers can be explained in terms of a slower exit rate of the longer fluorocarbon from its micelle.

Facilities and equipment are described for large-scale, long-term “nose-only” inhalation exposure of mice to whole cigarette smoke. Experimental procedures and equipment were designed to provide the mice with exposure conditions where [1] the lung was the major target organ for the smoke, [2] large quantities of fresh, whole cigarette smoke could be generated, [3] large numbers of animals could be exposed at one time, [4] routine, daily exposures could be given over a major portion of the lifetime of the animal, [5] monitoring and documentation of the quantity of smoke presented to the animals was provided during each exposure session, [6] safety systems were provided that assured exposure of the animals to smoke only under pre-set exposure conditions, and [7] cigarette smoke was generated under conditions where factors, such as cigarette type, smoke aerosol concentration and smoke particle size, were controlled.

Structural alterations in lipid membranes that are induced by changes in pH or by selective enzyme−substrate or antibody−antigen interactions can provide changes in fluorescence intensity from membranes containing nitrobenzoxadiazolyldipalmitoylphosphatidylethanolamine (NBD−PE). For example, fluorimetric responses of vesicles consisting of mixtures of phosphatidic acid (PA) and phosphatidylcholine (PC) prepared either from egg yolk or as synthetic, dipalmitoyl-substituted moieties and containing 2.3 mol % NBD−PE consist of either an increase or decrease in total fluorescence yield upon alteration of supporting electrolyte pH. This response was due to changes in NBD−PE self-quenching and the local environment of the fluorophore. The present work attempts to identify the factors that determine the fluorescence sensitivity of these lipid membranes. The impact of phosphatidic acid loading in vesicular bilayer lipid membranes and microscopic structural heterogeneity in monolayers at the air−water interface were explored. The results indicated that monolayers that exhibited laterally-separated phase domains on the microscopic scale provided enhanced sensitivity to perturbations of bulk pH and membrane surface charge redistribution through the alteration of the degree of headgroup ionization. Variations in the surface potential upon compression of either egg PA/egg PC or DPPA/DPPC monolayers in the liquid-expanded state were observed in order to facilitate the qualitative correlation of trends in the fluorimetric response of structurally homogeneous and structurally heterogeneous vesicular membranes with the existence of laterally-separated phase domains. The results indicated a strong correlation between sensitivity and structurally heterogeneity. The results also suggest the existence of ordered sub-microscopic domains in otherwise structurally homogeneous egg PA/egg PC membranes.

1. The thermal denaturation of DNA from rat liver was studied spectrophotometrically. In sodium phosphate buffers denaturation led to a single-stranded form having, at 25°, about 25% of the hypochromism of the intact double helix. 2. The hypochromism of the denatured form was the same in 1mm- as in 10mm-sodium phosphate buffer and was scarcely affected by reaction with formaldehyde. The hypochromism was decreased by about 40% in the presence of 8m-urea. 3. The hypochromism of denatured DNA at low ionic strengths was about the same as that of fragments of reticulocyte ribosomal RNA that were too short to form double-helical secondary structure and about the same as that of RNA after reaction with formaldehyde. 4. The spectrum of DNA was slightly affected by the presence of 8m-urea or 4m-guanidinium chloride. The differences in the spectrum of the native and denatured forms of DNA in 0·1m-sodium phosphate buffer, in 8m-urea–10mm-sodium phosphate buffer and in 4m-guanidinium chloride–10mm-sodium phosphate buffer, pH7·6, were similar but not identical. 5. Denatured rat liver DNA appears to have no double-helical character at 25° in 10mm-sodium phosphate buffer, pH7·6; increasing the buffer concentration to 0·1m leads to a more compact form in which about 40% of the residues form base pairs.

1. RNA isolated from the sub-units of rabbit reticulocyte ribosomes was hydrolysed by 0·4n-potassium hydroxide at 20°. The probability of main-chain scission was calculated from the number-average chain length, which was obtained from S25,w in 0·01m-phosphate buffer. 2. The fraction, f, of the original secondary structure that the fragments re-formed at neutral pH in 4m-guanidinium chloride, as well as in 0·01m- and 0·1m-phosphate buffer, was derived from changes in extinction over the range 220–310mμ on thermal denaturation. 3. The secondary structure of RNA is regarded as an assembly of hairpin loops each of 2N+b residues on average, where N is the number of base-paired residues and b is the number of unpaired residues. 4. If chain scission takes place at random then 2N+b=logf/log(1–p). 5. For RNA from the smaller sub-unit 2N+b was estimated as 25±5 residues, compared with 30±5 residues for the less stable species and 35±5 residues for the more stable species of hairpin loop of RNA from the larger sub-unit.

Leucyl-tRNA synthetase from bakers' yeast was purified to homogeneity and characterized. The native enzyme has a molecular weight of 120,000 and contains two identical subunits that upon dissociation display very low aminoacylation activity. From the molecular weight and the sedimentation coefficient of the native enzyme (s20,w0= 6.05 x10-13) a value of 5.18 x10-7was calculated for d20,w0, which leads to a Stokes radius of 40.7 A. For a spherical molecule this radius corresponds to a volume of 282,000 A3. The kinetic parameters for the enzyme with its substrates are typical for this class of enzymes.

1. Two species of double-helical RNA isolated from mycelium of Penicillium chrysogenum were titrated with acid at 25°C and 95°C (solvent 0.1m-sodium phosphate buffer). At 25°C denaturation occurred at about pH3. At 95°C in the denatured form cytosine residues titrated as a simple monobasic acid of pK3.9 compared with pK≃2.5 for the native form at 25°C. 2. On thermal denaturation in neutral and acidic solutions one species of RNA (38% rG·rC) ‘melted’ in three distinct stages, equivalent to a mixture of three species, namely one of about 25% rG·rC, another of about 33% rG·rC and a third of about 46% rG·rC: the relative proportions were 0.25:0.35:0.40. 3. On thermal denaturation in acidic solutions the increase in the fraction of ionized cytosine residues concomitant with the ‘melting’ of rG·rC base pair also affects the spectrum especially at 280nm and serves to enhance the contribution of rG·rC base pairs at this wavelength. The increment in ε(P) at 280nm on ‘melting’ an rG·rC base pair approaches 53501·mol−1·cm−1 depending on pH, compared with 33501·mol−1·cm−1 at pH7. In contrast ε(P) at 280nm is scarcely affected by ‘melting’ rA·rU base pairs or by the protonization of adenine residues. 4. Changes in the spectrum of Escherichia coli rRNA on denaturation in acidic solutions were studied to yield the mole fractions of rA·rU and rG·rC base pairs ‘melting’ at particular pH values.