Enhanced Antimicrobial Activity of Biocompatible Bacterial Cellulose Films via Dual Synergistic Action of Curcumin and Triangular Silver Nanoplates.

Curcumin and triangular silver nanoplates (TSNP)-incorporated bacterial cellulose (BC) films present an ideal antimicrobial material for biomedical applications as they afford a complete set of requirements, including a broad range of long-lasting potency and superior efficacy antimicrobial activity, combined with low toxicity. Here, BC was produced by Komagataeibacter medellinensis ID13488 strain in the presence of curcumin in the production medium (2 and 10%). TSNP were incorporated in the produced BC/curcumin films using ex situ method (21.34 ppm) and the antimicrobial activity was evaluated against Escherichia coli ATCC95922 and Staphylococcus aureus ATCC25923 bacterial strains. Biological activity of these natural products was assessed in cytotoxicity assay against lung fibroblasts and in vivo using Caenorhabditis elegans and Danio rerio as model organisms. Derived films have shown excellent antimicrobial performance with growth inhibition up to 67% for E. coli and 95% for S. aureus. In a highly positive synergistic interaction, BC films with 10% curcumin and incorporated TSNP have shown reduced toxicity with 80% MRC5 cells survival rate. It was shown that only 100% concentrations of film extracts induce low toxicity effect on model organisms' development. The combined and synergistic advanced anti-infective functionalities of the curcumin and TSNP incorporated in BC have a high potential for development for application within the clinical setting.

The phrenic nerve; the forgotten nerve in head and neck surgery.

BACKGROUND: Neck dissection is a commonly performed procedure for oncologic control of head and neck malignancy. With contemporary modified radical and selective neck dissections, haematoma, wound infection, tissue necrosis, chyle leak and injury involving the marginal mandibular, hypoglossal, vagus or accessory nerves are commonly described complications. Although the phrenic nerve courses within the surgical planes explored during a neck dissection and has a vital function in innervating the diaphragm, few studies have been performed to investigate the exact incidence of post-operative phrenic nerve paresis. This study aims to review the literature as to the rate of phrenic nerve injury following neck dissection. METHODS: A systematic literature review was conducted from 2000 to 2022 including studies reporting on phrenic nerve paresis following neck dissection. RESULTS: In total, 11 studies were included. The reported rate of immediate post-operative phrenic nerve paresis ranged from 0% to 5.3%, with an average rate of 0.613% (12/1959). The reported rate of phrenic nerve paresis at follow-up (1 month-127 months) ranged from 0% to 4.7%, with an average rate of 1.035% (5/483). There were no cases of bilateral phrenic nerve paresis reported in this period. CONCLUSIONS: Phrenic nerve paresis is an uncommon complication following neck dissection, often asymptomatic and potentially underreported. Bilateral phrenic nerve paresis is exceedingly rare. Injury can be avoided by staying superficial to the prevertebral fascia when dissecting around the anterior scalene muscle. Routine phrenic nerve integrity monitoring is not commonly utilized but may aid intra-operative phrenic nerve identification or confirmation of function.

Bilateral Maxillary and Mandibular Periapical Abscesses.

Odontogenic infections commonly arise from poor dental hygiene that forms dental caries, which can eventually progress to gingivitis and periodontitis. The authors present a case of facial swelling diagnosed as a periapical abscess with soft tissue swelling that extended into both the maxilla and mandible.

Using suction in back-bleeding conditions increases cement penetration without the need for a tourniquet.

BACKGROUND: The majority of total knee arthroplasties are performed with a tourniquet as it is perceived this gives rise to superior cement fixation. Tourniquets, however, have been associated with increased pain, post-operative swelling, and reduced knee range of movement which can all detrimentally impact patient recovery. This laboratory-based study aimed to assess if it is possible to achieve equivalent (or even enhanced) cementation without a tourniquet using a novel suction device. METHODS: Cement penetration was compared between conditions simulating bone with back-bleeding with and without the use of suction in open-cell rigid foam tibia models and porcine specimens. Suction was applied via a urinary catheter inserted into the tibial recess created for the implant's stem. Cement penetration depth was measured from micro-CT scans. The pull-off strength of cemented tibial implant analogues in porcine specimens with and without suction was also assessed. RESULTS: Suction gave rise to a significant (p = 0.028) increase in cement penetration depth in both the rigid foam, 5.4 - 6.6 mm, and porcine specimens, 0.7 - 1.0 mm. A non-significant increase in implant pull-off strength was also observed. CONCLUSION: Suction during cementation in a back-bleeding model resulted in significantly greater cement penetration depth. Using suction surgeons can avoid potential disadvantages of tourniquet use without compromising cementation.

Structural insights into serine-rich fimbriae from Gram-positive bacteria.

The serine-rich repeat family of fimbriae play important roles in the pathogenesis of streptococci and staphylococci. Despite recent attention, their finer structural details and precise adhesion mechanisms have yet to be determined. Fap1 (Fimbriae-associated protein 1) is the major structural subunit of serine-rich repeat fimbriae from Streptococcus parasanguinis and plays an essential role in fimbrial biogenesis, adhesion, and the early stages of dental plaque formation. Combining multidisciplinary, high resolution structural studies with biological assays, we provide new structural insight into adhesion by Fap1. We propose a model in which the serine-rich repeats of Fap1 subunits form an extended structure that projects the N-terminal globular domains away from the bacterial surface for adhesion to the salivary pellicle. We also uncover a novel pH-dependent conformational change that modulates adhesion and likely plays a role in survival in acidic environments.

Fixed bearing, all-polyethylene tibia, lateral unicompartmental arthroplasty - A final outcome study with up to 28 year follow-up of a single implant.

BACKGROUND: Lateral unicompartmental arthroplasty (UKA) constitutes only 5-10% of all unicompartmental replacements performed. Whilst the short and medium term benefits are well documented, there remains concern regarding the higher revision rate when compared with total knee replacement. We report the long term clinical outcome and survivorship of a large series of lateral UKA. PATIENTS AND METHODS: Between 1974 and 1994, 71 patients (82 knees) underwent a lateral fixed-bearing St Georg Sled UKA. Prospective data was collected pre-operatively and at regular intervals post-operatively using the Bristol Knee Score (BKS), with later introduction of the Oxford Knee (OKS) and Western Ontario MacMaster (WOMAC) scores. Kaplan Meier survival analysis was used, with revision, or need for revision, as end point. 85% of the patients were female. No patients were lost to follow-up. RESULTS: Functional knee scores improved post-operatively up to 10 years, at which point they demonstrated a steady decline. Survivorship was 72% at 15 years, and 68% at 20 and 25 years. Nineteen knees were revised, with progression of disease in another compartment the commonest reason. There were two revisions due to implant fracture. In patients aged over 70 years at time of index procedure, 81% died with a functioning prosthesis in situ. CONCLUSION: This represents the longest follow-up of a large series of lateral UKA. Results of this early design of fixed bearing UKA demonstrate satisfactory long term survivorship. In elderly patients, further intervention is rarely required. More contemporary designs or techniques may show improved long term survivorship in time.

Minimum 10-year outcomes of a fixed bearing all-polyethylene unicompartmental knee arthroplasty used to treat medial osteoarthritis.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) accounts for 8.9% of knee arthroplasty procedures in England, Wales and Northern Ireland. Fixed bearing UKA designs have shown favourable survivorship in registries when compared with mobile bearings but some studies suggest poor survival of all-polyethylene fixed tibial bearings. This study analyses long-term follow-up of patients with a medial fixed all-polyethylene tibial bearing UKA and reports survivorship and 10-year clinical outcomes. METHODS: Data was collected prospectively for 214 medial unicompartmental all-polyethylene tibial bearing UKAs implanted in 184 patients at our tertiary referral centre between November 2002 and December 2007. The indication was osteoarthritis in all but one patient. Patient reported outcome scores were documented pre-operatively and at five, eight, 10 and 12 years of follow-up. The mean patient age was 70 years (range 41-87). RESULTS: Outcome and survivorship data were collected for 214 medial all-polyethylene tibial bearing UKAs. There were outcomes recorded for 83 UKAs with at least 10-year follow-up. Twenty-four patients underwent revision of their UKA at an average of 5.84 years after the primary procedure. Kaplan-Meier analysis demonstrated survivorship of 89.1% at 10 years and the OKS, AKSS and WOMAC patient reported outcomes remained significantly improved in comparison to preoperatively. For those 70 years or older, 10-year survivorship was 92.4%, compared to 85.0% for those under 70 years old. CONCLUSION: Medial fixed all-polyethylene tibial bearing UKA demonstrates acceptable long-term survivorship and patient outcomes. It appears to be a suitable option for the treatment of medial compartment OA, particularly in older patients.

Two step porosification of biomimetic thin-film hydroxyapatite/alpha-tri calcium phosphate coatings by pulsed electron beam irradiation.

Here we show a new and effective methodology for rapid/controllable porosification of thin-film ceramics, which may be applied in medical devices/electronics and membrane nano-filtration. Dense hydroxyapatite applied to Ti6Al4V by plasma-assisted PVD was electron-beam irradiated to induce flash melting/boiling. Deposited coatings contained amorphous and nano-crystalline/stoichiometric hydroxyapatite (~35 nm). Irradiation (voltages 13-29 kV) led to ablation (up to 45% mass loss) and average/maximum pore areas from (0.07-1.66)/(0.69-92.53) µm2, mimicking the human cortical bone. Vitrification above 1150 °C formed (~62-30 nm) crystallites of α-Tri Calcium Phosphate. Unique porosification resulted from irradiation-induced sub-surface boiling and limited thermal conductivity of hydroxyapatite, causing material to expand/explode through the more quickly solidified top surface. Commercially applicable, roughened Ti6Al4V exacerbated the heating and boiling explosion phenomenon in certain regions, producing an array of pore sizes. Scaffold-like morphologies were generated by interconnection of micron/sub-micron porosity, showing great potential for facile generation of a biomimetic surface treatment for osseointegration.

Self-assembled adhesive biomaterials formed by a genetically designed fusion protein.

Here we report a recombinant protein (MS) obtained by genetic fusion of a mussel foot protein (Mfp3) motif into a silk spidroin (MaSp1). The MS not only self-assembled into a supramolecular fibre, as does the parent MaSp1, but also showed enhanced adhesiveness resulting from the DOPA-containing Mfp3 portion. The successful incorporation of the wet adhesiveness of Mfp3 into the well-structured assembly of MaSp1 may provide a new insight for the genetic design of underwater adhesive recombinant proteins by utilizing the structural features of a spidroin protein.

Self-Healable Supramolecular Hydrogel Formed by Nor-Seco-Cucurbit[10]uril as a Supramolecular Crosslinker.

A supramolecular hydrogel was formed by a simple mixing of solutions of nor-seco-cucurbit[10]uril (NS-CB[10]) and adamantylamine-terminated 4-armed polyethylene glycol (AdA-4-arm-PEG). In the formation of the hydrogel, NS-CB[10] acted as a noncovalent crosslinker to form a ternary complex with two AdA moieties. The dynamic and selective nature of the host-guest interaction between NS-CB[10] and AdA enabled the supramolecular hydrogel to rapidly recover its physical properties after it was damaged. In addition, the recovered hydrogel retained its physical properties with negligible differences from those of the pristine material, even after multiple self-healing cycles. The NS-CB[10]-based hydrogel with the self-healing property may be useful for various biological applications such as drug delivery, cell therapy and tissue engineering.

Targeting the PI3K/AKT/mTOR Pathway for the Treatment of Mesenchymal Triple-Negative Breast Cancer: Evidence From a Phase 1 Trial of mTOR Inhibition in Combination With Liposomal Doxorubicin and Bevacizumab.

IMPORTANCE: Triple-negative breast cancer (TNBC) classified by transcriptional profiling as the mesenchymal subtype frequently harbors aberrations in the phosphoinositide 3-kinase (PI3K) pathway, raising the possibility of targeting this pathway to enhance chemotherapy response. Up to 30% of mesenchymal TNBC can be classified histologically as metaplastic breast cancer, a chemorefractory group of tumors with a mixture of epithelial and mesenchymal components identifiable by light microscopy. While assays to identify mesenchymal TNBC are under development, metaplastic breast cancer serves as a clinically identifiable surrogate to evaluate potential regimens for mesenchymal TNBC. OBJECTIVE: To assess safety and efficacy of mammalian target of rapamycin (mTOR) inhibition in combination with liposomal doxorubicin and bevacizumab in patients with advanced metaplastic TNBC. DESIGN, SETTING, AND PARTICIPANTS: Phase 1 study with dose escalation and dose expansion at the University of Texas MD Anderson Cancer Center of patients with advanced metaplastic TNBC. Patients were enrolled from April 16, 2009, to November 4, 2014, and followed for outcomes with a cutoff date of November 1, 2015, for data analysis. INTERVENTIONS: Liposomal doxorubicin, bevacizumab, and the mTOR inhibitors temsirolimus or everolimus using 21-day cycles. MAIN OUTCOMES AND MEASURES: Safety and response. When available, archived tissue was evaluated for aberrations in the PI3K pathway. RESULTS: Fifty-two women with metaplastic TNBC (median age, 58 years; range, 37-79 years) were treated with liposomal doxorubicin, bevacizumab, and temsirolimus (DAT) (N = 39) or liposomal doxorubicin, bevacizumab, and everolimus (DAE) (N = 13). The objective response rate was 21% (complete response = 4 [8%]; partial response = 7 [13%]) and 10 (19%) patients had stable disease for at least 6 months, for a clinical benefit rate of 40%. Tissue was available for testing in 43 patients, and 32 (74%) had a PI3K pathway aberration. Presence of PI3K pathway aberration was associated with a significant improvement in objective response rate (31% vs 0%; P = .04) but not clinical benefit rate (44% vs 45%; P > .99). CONCLUSIONS AND RELEVANCE: Using metaplastic TNBC as a surrogate for mesenchymal TNBC, DAT and DAE had notable activity in mesenchymal TNBC. Objective response was limited to patients with PI3K pathway aberration. A randomized trial should be performed to test DAT and DAE for metaplastic TNBC, as well as nonmetaplastic, mesenchymal TNBC, especially when PI3K pathway aberrations are identified.

A collagen IV matrix is required for guinea pig gastric epithelial cell monolayers to provide an optimal model of the stomach surface for biopharmaceutical screening.

The surface epithelial cells of the stomach represent a major component of the gastric barrier. A cell culture model of the gastric epithelial cell surface would prove useful for biopharmaceutical screening of new chemical entities and dosage forms. Primary cultures of guinea pig gastric mucous epithelial cells were grown on filter inserts (Transwells) for 3 days. Tight-junction formation, assessed by transepithelial electrical resistance (TEER) and permeability of mannitol and fluorescein, was enhanced when collagen IV rather than collagen I was used to coat the polycarbonate filter. TEER for cells grown on collagen IV was close to that obtained with intact guinea pig gastric epithelium in vitro. Differentiation was assessed by incorporation of [3H]glucosamine into glycoprotein and by activity of NADPH oxidase, which produces superoxide. Both of these measures were greater for cells grown on filters coated with collagen I than for cells grown on plastic culture plates, but no major difference was found between cells grown on collagens I and IV. The proportion of cells, which stained positively for mucin with periodic acid Schiff reagent, was greater than 95% for all culture conditions. Monolayers grown on membranes coated with collagen IV exhibited apically polarized secretion of mucin and superoxide, and were resistant to acidification of the apical medium to pH 3.0 for 30 min. A screen of nonsteroidal anti-inflammatory drugs revealed a novel effect of diclofenac and niflumic acid in reversibly reducing permeability by the paracellular route. In conclusion, the mucous cell preparation grown on collagen IV represents a good model of the gastric surface epithelium suitable for screening procedures.

Highly efficient and selective phosphorylation of amino acid derivatives and polyols catalysed by 2-aryl-4-(dimethylamino)pyridine-N-oxides--towards kinase-like reactivity.

The chemoselective phosphorylation of hydroxyl containing amino acid derivatives and polyols by phosphoryl chlorides catalyzed by 2-aryl-4-(dimethylamino)pyridine-N-oxides is described.