Abdominal wall reconstruction using biosynthetic absorbable mesh in high-risk complex ventral hernia.

BACKGROUND: Biosynthetic mesh may represent an improvement on biological and large pore synthetic meshes for high-risk complex ventral hernia repair. This study aimed to evaluate the performance of polyglycolic acid (PGA):trimethylene carbonate (TMC) biosynthetic mesh for reinforcement of the midline fascial closure in a single-stage repair of complex ventral hernias in high-risk patients. METHODS: A retrospective review was undertaken for patients who underwent a planned open single-stage complex ventral hernia repair with a single unit of PGA:TMC biosynthetic mesh between May 2013 and August 2017. Data on outcome variables were recorded and quality of life assessed using the Short Form-12 (SF-12) instrument. RESULTS: Overall, 56 patients underwent abdominal wall reconstruction for complex ventral hernias. All meshes were placed in the retrorectus position. Some 39% underwent component separation. The majority of patients (86%, n = 48) had high risk (grade 2 or 3) hernias according to the Ventral Hernia Working Group classification. Overall hernia recurrence rate was 3.6% (n = 2). Postoperative surgical site infection occurred in 26.8% (n = 15). Median follow-up by clinical examination was 6 months (range 4–17). Median telephone follow-up was 21 months (range 4–54). Pre- and post-treatment SF-12 quality of life assessments demonstrated significant improvements in both the physical and mental components. CONCLUSION: This study reports a large series of abdominal wall reconstructions using biosynthetic mesh in complex ventral hernia. The findings indicate promising early outcome data associated with use of biosynthetic mesh. Larger well-controlled studies with longer follow-up are needed for confirmation of these findings.

Discovery of processive catalysis by an exo-hydrolase with a pocket-shaped active site.

Substrates associate and products dissociate from enzyme catalytic sites rapidly, which hampers investigations of their trajectories. The high-resolution structure of the native Hordeum exo-hydrolase HvExoI isolated from seedlings reveals that non-covalently trapped glucose forms a stable enzyme-product complex. Here, we report that the alkyl ß-D-glucoside and methyl 6-thio-ß-gentiobioside substrate analogues perfused in crystalline HvExoI bind across the catalytic site after they displace glucose, while methyl 2-thio-ß-sophoroside attaches nearby. Structural analyses and multi-scale molecular modelling of nanoscale reactant movements in HvExoI reveal that upon productive binding of incoming substrates, the glucose product modifies its binding patterns and evokes the formation of a transient lateral cavity, which serves as a conduit for glucose departure to allow for the next catalytic round. This path enables substrate-product assisted processive catalysis through multiple hydrolytic events without HvExoI losing contact with oligo- or polymeric substrates. We anticipate that such enzyme plasticity could be prevalent among exo-hydrolases.

Valleytronics: Opportunities, Challenges, and Paths Forward.

A lack of inversion symmetry coupled with the presence of time-reversal symmetry endows 2D transition metal dichalcogenides with individually addressable valleys in momentum space at the K and K' points in the first Brillouin zone. This valley addressability opens up the possibility of using the momentum state of electrons, holes, or excitons as a completely new paradigm in information processing. The opportunities and challenges associated with manipulation of the valley degree of freedom for practical quantum and classical information processing applications were analyzed during the 2017 Workshop on Valleytronic Materials, Architectures, and Devices; this Review presents the major findings of the workshop.

Degradation of Akt using protein-catalyzed capture agents.

Abnormal signaling of the protein kinase Akt has been shown to contribute to human diseases such as diabetes and cancer, but Akt has proven to be a challenging target for drugging. Using iterative in situ click chemistry, we recently developed multiple protein-catalyzed capture (PCC) agents that allosterically modulate Akt enzymatic activity in a protein-based assay. Here, we utilize similar PCCs to exploit endogenous protein degradation pathways. We use the modularity of the anti-Akt PCCs to prepare proteolysis targeting chimeric molecules that are shown to promote the rapid degradation of Akt in live cancer cells. These novel proteolysis targeting chimeric molecules demonstrate that the epitope targeting selectivity of PCCs can be coupled with non-traditional drugging moieties to inhibit challenging targets.

The influence of water on the optical properties of single-layer molybdenum disulfide.

Adsorbed molecules can significantly affect the properties of atomically thin materials. Physisorbed water plays a significant role in altering the optoelectronic properties of single-layer MoS2 , one such 2D film. Here the distinct quenching effect of adsorbed water on the photoluminescence of single-layer MoS2 is demonstrated through scanning-probe and optical microscopy.

Assessment of clinical outcomes of Roth and MBT bracket prescription using the American Board of Orthodontics Objective Grading System.

BACKGROUND: There is always a need to assess whether small changes in bracket prescription can lead to visually detectable differences in tooth positions. However, with little clinical evidence to show advantages of any of the popularly used bracket systems, orthodontists are forced to make clinical decisions with little scientific guidance. AIM: To compare the orthodontic cases finished with Roth and MBT prescription using American Board of Orthodontics-Objective Grading System (ABO-OGS). SETTINGS AND DESIGN: Department of Orthodontics, Post-graduate dental college, retrospective cross-sectional study. MATERIALS AND METHODS: Forty patients selected were divided into two groups of 20 patients each finished with straight wire appliance using Roth and MBT prescription, respectively. The examiner ability was assessed and calibrated by one of the ABO certified clinician to grade cases using the OGS. STATISTICAL ANALYSIS: Unpaired student t-test was used and P < 0.05 was accepted as significant. RESULTS AND CONCLUSIONS: MBT bracket group had a lower score of 2.60 points in buccolingual inclination and lower score of 1.10 points in occlusal contact category that was statistically significant when compared with Roth group. The difference in total ABO-OGS score was 2.65 points showing that the outcome for the MBT prescription was better than that of the Roth prescription, which is statistically significant, but with little or no clinical significance. It can be concluded that use of either one of the Roth and MBT bracket prescriptions have no impact to the overall clinical outcome and quality of treatment entirely depends on clinician judgment and experience.

The use of Gore Bio-A in the management of the open abdomen.

Non-permanent, non-woven options for the closure of an open abdomen have previously been limited to biologics such as Permacol or Strattice. Gore Bio-A is constructed from biocompatible synthetic fibres, the use of which has only been described in the repair of inguinal hernia, hiatal hernia and fistula-in-ano. A 60-year-old male underwent emergency laparotomy, partial gastrectomy and formation of a feeding jejunostomy for a strangulated and perforated intrathoracic hiatus hernia. His abdominal wall subsequently dehisced for which he underwent laparostomy and subsequent early closure with a Gore Bio-A mesh, secured in an onlay manner with 2/0 vicryl. Functional and cosmetic outcomes were satisfactory and the patient was discharged home. The use of Gore Bio-A is a safe, feasible and cost effective alternative to traditional biologics for the closure of a laparostomy, deployment of which is safe within a contaminated field. Further prospective data is needed to clarify its role.

High-throughput production and structural characterization of libraries of self-assembly lipidic cubic phase materials.

A protocol is presented for the high-throughput (HT) production of lyotropic liquid crystalline phases from libraries of lipids and lipid mixtures using standard liquid dispensing robotics, implementing methods that circumvent the problems traditionally associated with handling the highly viscous cubic phase. In addition, the ability to structurally characterize lipidic phases and assess functionality for membrane proteins contained within cubic phases, in a HT manner, is demonstrated. The techniques are combined and exemplified using the application of membrane protein crystallization within lipidic cubic phases.

Visualizing local doping effects of individual water clusters on gold(111)-supported graphene.

The local charge carrier density of graphene can exhibit significant and highly localized variations that arise from the interaction between graphene and the local environment, such as adsorbed water, or a supporting substrate. However, it has been difficult to correlate such spatial variations with individual impurity sites. By trapping (under graphene) nanometer-sized water clusters on the atomically well-defined Au(111) substrate, we utilize scanning tunneling microscopy and spectroscopy to characterize the local doping influence of individual water clusters on graphene. We find that water clusters, predominantly nucleated at the atomic steps of Au(111), induce strong and highly localized electron doping in graphene. A positive correlation is observed between the water cluster size and the local doping level, in support of the recently proposed electrostatic-field-mediated doping mechanism. Our findings quantitatively demonstrate the importance of substrate-adsorbed water on the electronic properties of graphene.

Efficiency, behavior, and clinical properties of superelastic NiTi versus multistranded stainless steel wires: a prospective clinical trial.

OBJECTIVE: To investigate efficiency, behavior, and properties of superelastic NiTi vs multistranded stainless steel wires in Begg and preadjusted edgewise appliance (PEA) under moderate to severe crowding conditions. MATERIAL AND METHODS: Ninety-six participants (48 male, 48 female), aged 12-18 years old (mean age  =  15.2 ± 1.95), with moderate (≤ 6 mm; mean  =  5.3 ± 0.48) to severe (> 6 mm; mean  =  7.9 ± 0.66) initial crowding were distributed into four groups: superelastic NiTi PEA (n  =  24), superelastic NiTi Begg (n  =  24), multistranded (coaxial) stainless steel PEA (n  =  25), and multistranded (coaxial) stainless steel Begg (n = 23). In this study, 0.16-inch superelastic (austenitic active) NiTi and 0.175-inch multistranded (six stranded, coaxial) stainless steel wires were used in a 0.022-inch slot (Roth prescription) PEA and Begg appliance with a follow-up of six weeks. RESULTS: Analysis of variance revealed no significant difference in reduction of crowding between superelastic NiTi PEA and multistranded (coaxial) stainless steel PEA groups, but reduction in crowding was significantly greater in the superelastic NiTi Begg group compared with the multistranded (coaxial) stainless steel Begg group with F (3, 44)  =  8.896, P < .001, and effect size (ω) 0.57 in moderate crowding and F (3, 44)  =  122.341, P < .001, and effect size (ω) 0.93 in severe crowding. Linear regression demonstrated significant (P < .05) positive correlation between amount of initial crowding and reduction in crowding in all groups except the multistranded (coaxial) stainless steel Begg group, wherein a negative correlation did exist. CONCLUSION: Superelastic NiTi performed significantly better than multistranded (coaxial) stainless steel wire in the Begg appliance. However, in PEA, there was no significant difference.

The microscopic structure of adsorbed water on hydrophobic surfaces under ambient conditions.

The interaction of water vapor with hydrophobic surfaces is poorly understood. We utilize graphene templating to preserve and visualize the microscopic structures of adsorbed water on hydrophobic surfaces. Three well-defined surfaces [H-Si(111), graphite, and functionalized mica] were investigated, and water was found to adsorb as nanodroplets (∼10-100 nm in size) on all three surfaces under ambient conditions. The adsorbed nanodroplets were closely associated with atomic-scale surface defects and step-edges and wetted all the hydrophobic substrates with contact angles<∼10°, resulting in total water adsorption that was similar to what is found for hydrophilic surfaces. These results point to the significant differences between surface processes at the atomic/nanometer scales and in the macroscopic world.

Laparoscopic preperitoneal mesh repair using a novel self-adhesive mesh.

Prosthetic mesh is now used routinely in inguinal hernia repairs, although its fixation is thought to be a potential cause of chronic groin pain. The Parietene ProGrip™ (TYCO Healthcare) mesh, which is semi-resorbable and incorporates self-fixing properties, has been shown to provide satisfactory repair in open surgery. We describe the use of this mesh in TAPP hernia repair, which has not previously been reported in the literature. A prospective study of 29 patients showed a mean operative time to be 47.6 min, with 96% of patients discharged home on the day of surgery or the day after. Visual analog pain scales (out of 10) reduced from 4 preoperatively to 0 at 6 months, and only 1 patient suffered a minor wound complication. The use of this mesh in transabdominal preperitoneal hernia repair is therefore feasible, safe, and may reduce postoperative pain.

Atomic force microscopy characterization of room-temperature adlayers of small organic molecules through graphene templating.

We report on the use of graphene templating to investigate the room-temperature structure and dynamics of weakly bound adlayers at the interfaces between solids and vapors of small organic molecules. Monolayer graphene sheets are employed to preserve and template molecularly thin adlayers of tetrahydrofuran (THF) and cyclohexane on atomically flat mica substrates, thus permitting a structural characterization of the adlayers under ambient conditions through atomic force microscopy. We found the first two adlayers of both molecules adsorb in a layer-by-layer fashion, and atomically flat two-dimensional islands are observed for both the first and the second adlayers. THF adlayers form initially as rounded islands but, over a period of weeks, evolve into faceted islands, suggesting that the adlayers possess both liquid and solid properties at room temperature. Cyclohexane adlayers form crystal-like faceted islands and are immobile under the graphene template. The heights of the second adlayers of THF and cyclohexane are measured to be 0.44 ± 0.02 and 0.50 ± 0.02 nm, respectively, in good agreement with the layer thicknesses in the monoclinic crystal structure of THF and the Phase I "plastic crystal" structure of cyclohexane. The first adlayers appear slightly thinner for both molecules, indicative of interactions of the molecules with the mica substrate.

Crystal structure of the amyloid-ß p3 fragment provides a model for oligomer formation in Alzheimer's disease.

Alzheimer's disease is a progressive neurodegenerative disorder associated with the presence of amyloid-ß (Aß) peptide fibrillar plaques in the brain. However, current evidence suggests that soluble nonfibrillar Aß oligomers may be the major drivers of Aß-mediated synaptic dysfunction. Structural information on these Aß species has been very limited because of their noncrystalline and unstable nature. Here, we describe a crystal structure of amylogenic residues 18-41 of the Aß peptide (equivalent to the p3 α/γ-secretase fragment of amyloid precursor protein) presented within the CDR3 loop region of a shark Ig new antigen receptor (IgNAR) single variable domain antibody. The predominant oligomeric species is a tightly associated Aß dimer, with paired dimers forming a tetramer in the crystal caged within four IgNAR domains, preventing uncontrolled amyloid formation. Our structure correlates with independently observed features of small nonfibrillar Aß oligomers and reveals conserved elements consistent with residues and motifs predicted as critical in Aß folding and oligomerization, thus potentially providing a model system for nonfibrillar oligomer formation in Alzheimer's disease.

Reduction of thermal conductivity in phononic nanomesh structures.

Controlling the thermal conductivity of a material independently of its electrical conductivity continues to be a goal for researchers working on thermoelectric materials for use in energy applications and in the cooling of integrated circuits. In principle, the thermal conductivity κ and the electrical conductivity σ may be independently optimized in semiconducting nanostructures because different length scales are associated with phonons (which carry heat) and electric charges (which carry current). Phonons are scattered at surfaces and interfaces, so κ generally decreases as the surface-to-volume ratio increases. In contrast, σ is less sensitive to a decrease in nanostructure size, although at sufficiently small sizes it will degrade through the scattering of charge carriers at interfaces. Here, we demonstrate an approach to independently controlling κ based on altering the phonon band structure of a semiconductor thin film through the formation of a phononic nanomesh film. These films are patterned with periodic spacings that are comparable to, or shorter than, the phonon mean free path. The nanomesh structure exhibits a substantially lower thermal conductivity than an equivalently prepared array of silicon nanowires, even though this array has a significantly higher surface-to-volume ratio. Bulk-like electrical conductivity is preserved. We suggest that this development is a step towards a coherent mechanism for lowering thermal conductivity.

Alzheimer's amyloid-beta rescues yeast from hydroxide toxicity.

Amyloid-beta(Abeta42), which is known to be toxic to neuronal cells, protects yeast cells from severe sodium hydroxide toxicity. More than 85% cell death was caused by treatment with 1 mM NaOH and approximately 95% was observed at a 2 mM concentration. However, greater than 55% cells survived the treatment in the presence of Abeta42. A strong protective effect of the peptide was also evident from the differential staining of the treated culture with propidium iodide.

Validation of folate in a convenient yeast assay suited for identification of inhibitors of Alzheimer's amyloid-beta aggregation.

Previously in the search for chemopreventatives for Alzheimer's disease (AD), microbial cells with amyloid-beta (Abeta) protein fusions have been used to screen for compounds that reduce the aggregation, misfolding or oligomerization of Abeta. In the current study, such a system has been used to look at the effect of folate, whose deficiency has been associated with AD. A folate-deficient yeast strain producing Abeta fused to green fluorescent protein (GFP) that spontaneously misfolds/aggregates and suppresses green fluorescence was used to examine the effects of folinic acid on Abeta-GFP fluorescence. At levels that did not affect growth or plasmid stability, increasing levels of folinic acid led to increasing green fluorescence, suggesting folate can assist with preventing Abeta-misfolding/aggregation. This result supports a protective role for folate and suggests that yeast assays may provide significant new approaches for testing of AD chemopreventatives.

Substrate mediated reduction of copper-amyloid-beta complex in Alzheimer's disease.

X-Ray absorption near-edge spectroscopy (XANES) has been used to probe the substrate mediated reduction of Cu(2+) in Abeta-Cu(2+) complexes by ascorbate and the neurotoxin 6-hydroxydopamine (6-OHDA), however dopamine and, in particular, cholesterol are incapable of reducing soluble monomeric Abeta-Cu(2+) complexes.

The structure of the amyloid-beta peptide high-affinity copper II binding site in Alzheimer disease.

Neurodegeneration observed in Alzheimer disease (AD) is believed to be related to the toxicity from reactive oxygen species (ROS) produced in the brain by the amyloid-beta (Abeta) protein bound primarily to copper ions. The evidence for an oxidative stress role of Abeta-Cu redox chemistry is still incomplete. Details of the copper binding site in Abeta may be critical to the etiology of AD. Here we present the structure determined by combining x-ray absorption spectroscopy (XAS) and density functional theory analysis of Abeta peptides complexed with Cu(2+) in solution under a range of buffer conditions. Phosphate-buffered saline buffer salt (NaCl) concentration does not affect the high-affinity copper binding mode but alters the second coordination sphere. The XAS spectra for truncated and full-length Abeta-Cu(2+) peptides are similar. The novel distorted six-coordinated (3N3O) geometry around copper in the Abeta-Cu(2+) complexes include three histidines: glutamic, or/and aspartic acid, and axial water. The structure of the high-affinity Cu(2+) binding site is consistent with the hypothesis that the redox activity of the metal ion bound to Abeta can lead to the formation of dityrosine-linked dimers found in AD.

Structural rationale for low-nanomolar binding of transition state mimics to a family GH3 beta-D-glucan glucohydrolase from barley.

The interactions of a transition state mimic anilinomethyl glucoimidazole (AmGlcIm), with a K(i) constant of 0.6 x 10(-)(9) M and a Gibbs free energy value of -53.5 kJ/mol, with a family GH3 beta-d-glucan glucohydrolase from barley have been analyzed crystallographically and by ab initio quantum mechanical modeling. AmGlcIm binds 3 times more tightly to the beta-d-glucan glucohydrolase than a previously investigated phenyl glucoimidazole. In the enzyme-AmGlcIm complex, an additional residue, Tyr253, and a water molecule positioned between subsites -1 and +1 are recruited for binding. Analyses of the two binary complexes reveal the following. (i) An intricate network exists in which hydrogen bonds between the enzyme's catalytic pocket residues Lys206, His207, Tyr253, Asp285, and Glu491 and the glucoimidazoles are shorter by 0.15-0.53 A, compared with distances of hydrogen bonds in the Michaelis complex. (ii) The "glucose" moiety of the glucoimidazoles adopts a (4)E conformation that is vital for the low-nanomolar binding. (iii) The N1 atoms of the glucoimidazoles are positioned nearly optimally for in-line protonation by the Oepsilon1 atom of the catalytic acid/base Glu491. (iv) The enzyme derives binding energies from both glycone and aglycone components of the glucoimidazoles. (iv) The prevalent libration motion of the two domains of the enzyme could play a significant role during induced fit closure in the active site. (v) Modeling based on the structural data predicts that protons could be positioned on the N1 atoms of the glucoimidazoles, and the catalytic acid/base Glu491 could carry an overall negative charge. (vi) The enzyme-AmGlcIm complex reveals the likely structure of an early transition state during hydrolysis. Finally, the high-resolution structures enabled us to define minimal structures of oligosaccharides attached to Asn221, Asn498, and Asn600 N-glycosylation sites.