Decreasing Colectomy Rates in Advanced Adenomas.

Advanced colon adenomas are commonly treated with colectomy, which is associated with substantial morbidity and mortality. Novel endoscopic resection techniques have been described, including endoscopic mucosal resection (EMR) and endoscopic submucosal resection (ESR), which demonstrate promise in treating these neoplasms without colectomy. We performed a retrospective review of patients with advanced adenomas who were referred to a colorectal surgeon for evaluation for resection over 4 years. 40 of 46 (87%) of these patients underwent a successful endoscopic resection. 10 of 46 (21.6%) patients ultimately underwent an operation for a variety of reasons: inability to resect endoscopically (n = 6), invasive cancer on the excised specimen (n = 2), complication of procedure (n = 1), colectomy after polyp recurrence (n = 1). Our study demonstrates EMR and ESD offers an alternative to colectomy in appropriately selected patients with a high success rate. As more surgeons learn advanced endoscopic techniques, there is potential to decrease colectomy rates in benign disease.

Robotic Repair of a Symptomatic Perineal Hernia With Self-Fixating Synthetic Mesh.

Primary acquired perineal hernias are rare defects through the pelvic floor diaphragm. The optimal surgical technique for repair remains unknown, and recurrence rates approach 50%. We present a 65-year-old female without previous obstetric or pelvic surgical history who was found to have herniated sigmoid colon through a 2×2 cm levator ani defect. The patient underwent robotic transabdominal hernia repair with a synthetic self-fixating underlay mesh. The peritoneum was primarily closed and the patient was discharged the same day. There is no sign of recurrence to date. Our minimally invasive approach with extraperitoneal mesh placement provided us with several advantages: ambulatory surgery; excellent visualization of the defect; easier suturing in the deep pelvis compared to traditional laparoscopy; and mesh reinforcement while minimizing the risks of erosion, migration, adhesion, and fistula formation.

Managing an adult CF population in the COVID-19 pandemic-1 year on.

BACKGROUND: The advent of the COVID-19 pandemic in 2020 required an alteration in the routine care of people with CF (pwCF), deemed to be extremely vulnerable. AIM: We wished to report the alterations in clinical practice, including the introduction of remote video-assisted clinics, made to manage the adult pwCF attending our large centre. METHODS: We studied clinical records over a period of 2 years (March 2019 to February 2021) by comparing 19th March to 20th February (Y1) with 20th March to 21st February (Y2). RESULTS: We have shown out of hospital Multi Disciplinary Team (MDT) support increased and a greater proportion of IV therapy was administered at home. The VAC model of care increased clinical activity while reducing clinic non-attendance rates, suggesting more individuals engage with their carers. CONCLUSIONS: This new model of care has allowed greater engagement with pwCF.

Rapid whole cell imaging reveals a calcium-APPL1-dynein nexus that regulates cohort trafficking of stimulated EGF receptors.

The endosomal system provides rich signal processing capabilities for responses elicited by growth factor receptors and their ligands. At the single cell level, endosomal trafficking becomes a critical component of signal processing, as exemplified by the epidermal growth factor (EGF) receptors. Activated EGFRs are trafficked to the phosphatase-enriched peri-nuclear region (PNR), where they are dephosphorylated and degraded. The details of the mechanisms that govern the movements of stimulated EGFRs towards the PNR, are not completely known. Here, exploiting the advantages of lattice light-sheet microscopy, we show that EGFR activation by EGF triggers a transient calcium increase causing a whole-cell level redistribution of Adaptor Protein, Phosphotyrosine Interacting with PH Domain And Leucine Zipper 1 (APPL1) from pre-existing endosomes within one minute, the rebinding of liberated APPL1 directly to EGFR, and the dynein-dependent translocation of APPL1-EGF-bearing endosomes to the PNR within ten minutes. The cell spanning, fast acting network that we reveal integrates a cascade of events dedicated to the cohort movement of activated EGF receptors. Our findings support the intriguing proposal that certain endosomal pathways have shed some of the stochastic strategies of traditional trafficking and have evolved processes that provide the temporal predictability that typify canonical signaling.

Robotic inguinal lymph node dissection for melanoma: a novel approach to a complicated problem.

BACKGROUND: Indications for superficial inguinal lymph node (ILN) dissection in melanoma include fine needle aspiration or clinically positive ILN and sentinel lymph nodes (SLN). Open inguinal lymphadenectomy may be complicated by poor wound healing, deep vein thrombosis, and lymphedema. Technical considerations and case series of a novel surgical approach, robotic inguinal lymphadenectomy, are presented. METHODS: This is a case series of four robotic ILN dissections for melanoma at a tertiary care facility. Each patient had previously diagnosed melanoma by lymph node biopsy. Physician and patient jointly decided on robotic procedure after disclosure of this novel approach. Demographic, complication, pathological outcome, estimated blood loss (EBL), operative time, and length of stay (LOS) data were collected. RESULTS: No cases were aborted due to technical difficulty. The median patient age was 44.5 years (range 22-53 years) and median BMI was 27.5 (range 20.4-40.2). Operative time range was 120-231 min and EBL from 0 to 100 mL. Median nodal count was 5.5 (range 1-14 nodes). Patient LOS ranged from 0 (discharged from post anesthesia care unit) to 96 h. There was one complication of port site cellulitis, one seroma formation, and no instances of lymphedema. To date, there have been no deaths or melanoma recurrences in this population. CONCLUSION: Recent data suggest a minimum node count of six to seven for inguinal dissection. Of our four dissections, two were above this threshold and there were minimal postoperative complications. Given our limited sample size, future focus should be on increasing the data on this approach to optimize surgical outcomes and oncologic results.

Evaluating Surgery Resident Technical Skills: Intestinal Anastomosis in a Porcine Model.

Because work hour restrictions and technological developments such as staplers change the surgical landscape, efficient resident training methods are necessary to ensure surgical quality. This study evaluates efficacy of a porcine skills laboratory for teaching surgery residents to perform handsewn intestinal anastomoses based on a validated subjective tool and novel objective measurements. We hypothesized that resident performance would improve postintervention; junior residents would improve more than the seniors would. This prospective study was completed over a period of four months in 2015. Participants performed standardized two-layer, handsewn, end-to-end small intestine anastomosis in a live porcine model before (pretest) and after (posttest) an educational intervention. The intervention consisted of an instructional module and skills laboratory teaching session by attending surgeons. Participants were evaluated based on objective measurements of the anastomosis and blinded video evaluations using objective structured assessment of technical skills. Twenty-eight residents in a six-year general surgery program started and completed the study. The objective structured assessment of technical skills ratings demonstrated that the whole resident cohort had statistically significant improvement in pre- to posttest scores, 11.16 to 24.59 (P < 0.001). Junior and senior residents improved independently, 9.59 versus 22.53 (P < 0.001) and 13.59 versus 27.77 (P < 0.001), respectively. Finally, the cohort significantly improved in number of full-thickness Lembert sutures (2.36 vs 0.93, P = 0.001) and time to completion (31.28 vs 28.2 minutes, P = 0.046). Anastomotic leak pressure, anastomotic narrowing, and anastomotic tensile strength all trended toward improvement. A structured educational intervention, teaching intestinal anastomosis in a live porcine model produced significant improvement in residents' technical skills.

Atomic layer deposition of titanium dioxide on cellulose acetate for enhanced hemostasis.

TiO2 films may be used to alter the wettability and hemocompatibility of cellulose materials. In this study, pure and stoichiometric TiO2 films were grown using atomic layer deposition on both silicon and cellulose substrates. The films were grown with uniform thicknesses and with a growth rate in agreement with literature results. The TiO2 films were shown to profoundly alter the water contact angle values of cellulose in a manner dependent upon processing characteristics. Higher amounts of protein adsorption indicated by blurry areas on images generated by scanning electron microscopy were noted on TiO2 -coated cellulose acetate than on uncoated cellulose acetate. These results suggest that atomic layer deposition is an appropriate method for improving the biological properties of hemostatic agents and other blood-contacting biomaterials.

Atomic layer deposition and abrupt wetting transitions on nonwoven polypropylene and woven cotton fabrics.

Atomic layer deposition (ALD) of aluminum oxide on nonwoven polypropylene and woven cotton fabric materials can be used to transform and control fiber surface wetting properties. Infrared analysis shows that ALD can produce a uniform coating throughout the nonwoven polypropylene fiber matrix, and the amount of coating can be controlled by the number of ALD cycles. Upon coating by ALD aluminum oxide, nonwetting hydrophobic polypropylene fibers transition to either a metastable hydrophobic or a fully wetting hydrophilic state, consistent with well-known Cassie-Baxter and Wenzel models of surface wetting of roughened surfaces. The observed nonwetting/wetting transition depends on ALD process variables such as the number of ALD coating cycles and deposition temperature. Cotton fabrics coated with ALD aluminum oxide at moderate temperatures were also observed to transition from a natural wetting state to a metastable hydrophobic state and back to wetting depending on the number of ALD cycles. The transitions on cotton appear to be less sensitive to deposition temperature. The results provide insight into the effect of ALD film growth mechanisms on hydrophobic and hydrophilic polymers and fibrous structures. The ability to adjust and control surface energy, surface reactivity, and wettability of polymer and natural fiber systems using atomic layer deposition may enable a wide range of new applications for functional fiber-based systems.

Electroweak parity-violating energy shifts of amino acids: the "conformation problem".

The preceding paper described our coupled-perturbed Hartree-Fock (CPHF) and density functional theory (DFT) methods of computing the parity-violating energy shift (PVES). This paper addresses the "conformation problem"-the difficulty determining which hand of amino acids in solution is favoured by the weak force due to the difficulty determining the solution conformation. We attempt to resolve this by using the methods of the preceding paper to compute the PVES of solution and gas-phase amino acid structures determined by other groups from high level optimizations that include solvation. We conclude that the conformational hypersensitivity of the PVES still precludes a definite conclusion as to the sign of the PVES of L-alanine in solution, but that there is no problem in the gas phase: the PVES of gas-phase L-alanine is decisively negative. We show that the PVES is very sensitive to certain torsion angles, but is not hypersensitive to bondlengths or bond angles. In determining structures for PVES computations, there is therefore no need for expensive full optimizations: one can just optimize the crucial torsion angles. We present new computations of gas-phase amino acids PVESs, using partial optimizations with small basis sets, and the results agree well with those from higher level techniques. In the following paper we apply these less costly techniques to larger amino acids. The "conformation problem" has led some to dismiss the PVES as the source of life's handedness, but we believe this is premature: we show here that amino acids are a special case because their favoured conformations are almost achiral.

Evaluation of coupled perturbed and density functional methods of computing the parity-violating energy difference between enantiomers.

We present new coupled-perturbed Hartree-Fock (CPHF) and density functional theory (DFT) computations of the parity-violating energy difference (PVED) between enantiomers for H(2)O(2) and H(2)S(2). Our DFT PVED computations are the first for H(2)S(2) and the first with the new HCTH and OLYP functionals. Like other "second generation" PVED computations, our results are an order of magnitude larger than the original "first generation" uncoupled-perturbed Hartree-Fock computations of Mason and Tranter. We offer an explanation for the dramatically larger size in terms of cancellation of contributions of opposing signs, which also explains the basis set sensitivity of the PVED, and its conformational hypersensitivity (addressed in the following paper). This paper also serves as a review of the different types of "second generation" PVED computations: we set our work in context, comparing our results with those of four other groups, and noting the good agreement between results obtained by very different methods. DFT PVEDs tend to be somewhat inflated compared to the CPHF values, but this is not a problem when only sign and order of magnitude are required. Our results with the new OLYP functional are less inflated than those with other functionals, and OLYP is also more efficient computationally. We therefore conclude that DFT computation offers a promising approach for low-cost extension to larger biosystems, especially polymers. The following two papers extend to terrestrial and extra-terrestrial amino acids respectively, and later work will extend to polymers.

Parity-violating energy shifts of Murchison L-amino acids are consistent with an electroweak origin of meteorite L-enantiomeric excesses.

In 1996, four alpha-methyl amino acids in the Murchison meteorite--L-isovaline, L-alpha-methylnorvaline, L-alpha-methyl-allo-isoleucine and L-alpha-methyl-isoleucine--were found to show significant enantiomeric excesses of the L form, ranging from 2% to 9%. Their deuterium to hydrogen isotope ratios suggest they formed in the pre-solar interstellar gas cloud rather than during a later aqueous processing phase on the asteroid parent body. In this paper we apply the techniques of the preceding two papers to compute the parity-violating energy shifts of these amino acids. We find that, in the gas phase, the PVESs of the neutral L forms of all four Murchison alpha-methyl amino acids are decisively negative, and there is even some correlation between the magnitudes of the L-excesses and the magnitudes of the PVESs--all of which is at least consistent with an electroweak origin of the Murchison enantiomeric excesses.

Atomic layer deposition and biocompatibility of titanium nitride nano-coatings on cellulose fiber substrates.

Atomic layer deposition (ALD) is investigated as a process to produce inorganic metallic bio-adhesive coatings on cellulosic fiber substrates. The atomic layer deposition technique is known to be capable of forming highly conformal and uniform inorganic thin film coatings on a variety of complex surfaces, and this work presents an initial investigation of ALD on porous substrate materials to produce high-precision biocompatible titanium oxynitride coatings. X-ray photoelectron spectroscopy (XPS) confirmed TiNOx composition, and transmission electron microscopy (TEM) analysis showed the coatings to be uniform and conformal on the fiber surfaces. Biocompatibility of the modified structures was determined as a function of coating layer thickness by fluorescent live/dead staining of human adipose-derived adult stem cells (hADSC) at 6, 12 and 24 h. Cell adhesion showed that thin TiNOx coatings yielded the highest number of cells after 24 h with a sample coated with a 20 A coating having approximately 28.4 +/- 3.50 ng DNA. By altering the thickness of the deposited film, it was possible to control the amount of cells adhered to the samples. This work demonstrates the potential of low temperature ALD as a surface modification technique to produce biocompatible cellulose and other implant materials.

Atomic layer deposition of conformal inorganic nanoscale coatings on three-dimensional natural fiber systems: effect of surface topology on film growth characteristics.

Atomic-scale material deposition is utilized to achieve uniform coverage and modification of the surface properties of natural fiber and woven fabric materials, where irregular nanoscale features are embedded in a macroscale interpenetrating fiber network. The complex surface topology of the woven fabric results in significantly different film-growth thickness per ALD cycle as compared to planar surfaces coated using the same process conditions, likely due to reactant adsorption within the fiber starting material, as well as impeded reactant transport out of the fabric system during the purge cycle. Cotton textiles modified with conformal nanoscale Al2O3 are found to show extreme hydrophobic effects, distinctly different from planar surfaces that receive the same coatings. The results highlight key concerns for achieving controlled conformal coatings on complex surfaces and open the possibility for new textile finishing approaches to create novel fabric-based materials with specialized function and performance.

Atomic layer deposition on electrospun polymer fibers as a direct route to AL2O3 microtubes with precise wall thickness control.

Atomic layer deposition (ALD) of Al2O3 on electrospun poly(vinyl alcohol) microfiber templates is demonstrated as an effective and robust strategy by which to fabricate long and uniform metal-oxide microtubes. The wall thickness is shown to be precisely controlled within a molecular layer or so by adjusting the number of ALD cycles utilized. By judicious selection of the electrospinning and ALD parameters, designer tubes of various sizes and inorganic materials can be synthesized.

Evaluation of abnormal liver function tests.

Interpretation of abnormalities in liver function tests is a common problem faced by clinicians. This has become more common with the introduction of automated routine laboratory testing. Not all persons with one or more abnormalities in these tests actually have liver disease. The various biochemical tests, their pathophysiology, and an approach to the interpretation of abnormal liver function tests are discussed in this review.

Retention of fluorescent probes during aldehyde-free anhydrous freeze-substitution.

Fluorescent probes are widely used for microscopy of live-cell processes, but few such probes can also be used with classically fixed or otherwise immobilized material, and none has been used without aldehyde fixation, which can introduce artefacts of structure and probe localization. Here we show that the fluorescence patterns in fungal hyphae loaded with chloromethyl aminocoumarin (CMAC), and then anhydrously freeze-substituted, without any aldehyde fixation, are similar to those seen in living hyphae. Probe loss into the mounting medium (Spurr's resin) with CMAC and five other probes tested indicated that some unwanted solubilization of probe occurred during embedding, but nevertheless vacuoles could be imaged by their retention of probe.

Histological changes associated with the use of intravenous cyclosporin in the treatment of severe ulcerative colitis may mimic dysplasia.

BACKGROUND: During six years experience of intravenous cyclosporin (i.v. Cy) for severe ulcerative colitis we have noted that changes of villous architecture and epithelial regeneration occur even when the disease fails to enter clinical remission and colectomy is required. OBJECTIVE: To describe the histological changes in patients who received i.v. Cy and steroids compared with those treated with i.v. steroids alone. PATIENTS AND METHODS: Two groups of histological sections were reviewed. The first group was of 23 colectomy specimens from patients who had been treated with i.v. Cy and steroids. For 11 patients pre-Cy histological sections were available. The second group was of 10 colectomy specimens from patients who had received i.v. steroids alone. Biopsies were scored for their histological disease activity (HDAI), villous architecture and epithelial regeneration. The HDAI assesses the degree of acute and chronic inflammation. RESULTS: The post-Cy group had higher median scores for villous architecture and epithelial regeneration compared to the pre-Cy and poststeroid groups. For the patients where both pre- and post-Cy histological sections were available 63% increased their villous score post-Cy and 82% increased their epithelial regeneration score post-Cy. CONCLUSION: Although villous transformation and epithelial regeneration may be seen in UC they are more frequent and more severe in those patients who received i.v. Cy and i.v. steroids, compared to controls who received i.v. steroids alone. These histological changes may mimic dysplasia. Increased awareness of this potential mimic of dysplasia is crucial for patient management.