α‐Substitution Effects on the Ease of S→N‐Acyl Transfer in Aminothioesters

In S‐acylcysteines and homocysteines, the efficacy and rate of S→N‐acyl transfer (5 and 6 cyclic TSs) vary with the size of S‐acyl group. Conformational and quantum chemical calculations indicate that the spatial distance, b(N‐C), between the terminal amine and the thioester carbon is shortened by α‐C(O)X (X = OH, OMe, NH₂) substituents.     

Radiofrequency-generated glow discharge treatment: potential benefits for polyester ligaments

 This multicenter study has revealed that treating a woven polyethylene terephthalate (polyester) ligament with a radiofrequency (RF)-generated glow discharge (RFGD) produces marked benefits in terms of increased cell attachment and proliferation on the implant surface. In vitro tests of the same material revealed that the number of synovial fibroblasts attached to the treated samples after 14 days was four times that of the untreated material. Many of the cells were spread over the surface of a single filament, and some formed bridges between one filament and the next. The incorporation of [³H]-thymidine by synovial stromal cells (a measure of the amount of cell division) growing on the treated material was five times that on the untreated samples. The amount of DNA present on the treated material was also found to be almost an order of magnitude greater than that on untreated samples. This increase in cell attachment and proliferation is almost certainly related to a notable increase in wettability of the polyester surface induced by treatment. Mechanical tests revealed that, for ligaments with a nominal ultimate tensile strength of 2100 N, RF-generated glow treatment reduced the ligament's strength by 12% but increased its stiffness by 15%. After a medium-term fatigue test (10.8 million cycles), however, there appeared to be recovery of the mechanical properties, with the strength and stiffness of untreated and treated samples being essentially the same. After exhaustive fatigue tests (more than 62 million cycles) the residual strength of the treated ligaments was only 9% lower than that of the unfatigued and untreated ligaments. Received: July 1, 2002 / Accepted: October 22, 2002 Acknowledgments. The authors thank Xiros plc for providing ligament samples. We also thank the following individuals for their contribution to the work described in this study: Mr. Les Johnson, School of Textile Industries, University of Leeds, for carrying out wettability tests; Dr. David Woolley, Department of Medicine, University of Manchester for supplying cells for the study at Yorkshire Regional Tissue Bank; Mr. John Tresnan, Xiros plc, for carrying out the mechanical tests. We especially acknowledge the contribution of Sangjin Kang to the work carried out at the School of Biochemistry and Molecular Biology, University of Leeds. Offprint requests to: J.R.J. Rowland     

First-Principles Simulation of Dielectric Function in Biomolecules

The dielectric spectra of complex biomolecules reflect the molecular heterogeneity of the proteins and are particularly important for the calculations of electrostatic (Coulomb) and electrodynamic (van der Waals) interactions in protein physics. The dielectric response of the proteins can be decomposed into different components depending on the size, structure, composition, locality, and environment of the protein in general. We present a new robust simulation method anchored in rigorous ab initio quantum mechanical calculations of explicit atomistic models, without any indeterminate parameters to compute and gain insight into the dielectric spectra of small proteins under different conditions. We implement this methodology to a polypeptide RGD-4C (1FUV) in different environments, and the SD1 domain in the spike protein of SARS-COV-2. Two peaks at 5.2–5.7 eV and 14.4–15.2 eV in the dielectric absorption spectra are observed for 1FUV and SD1 in vacuum as well as in their solvated and salted models.     

Impact of biliary complications on quality of life in live-donor liver transplant recipients

BACKGROUND Despite significant advancements in liver transplantation(LT) surgical procedures and perioperative care, post-LT biliary complications(BCs) remain a significant source of morbidity, mortality, and graft failure. In addition, data are conflicting regarding the health-related quality of life(HRQoL) of LT recipients. Thus, the success of LT should be considered in terms of both the survival and recovery of HRQoL.AIM To assess the impact of BCs on the HRQoL of live-donor LT recipients(LDLT-Rs).METHODS We retrospectively analysed data for 25 LDLT-Rs who developed BCs post-LT between January 2011 and December 2016 at our institution. The Short Form 12 version 2(SF 12 v2) health survey was used to assess their HRQoL. We also included 25 LDLT-Rs without any post-LT complications as a control group.RESULTS The scores for HRQoL of LDLT-Rs who developed BCs were significantly higher than the norm-based scores in the domains of physical functioning(P = 0.003),role-physical(P 0.001), bodily pain(P = 0.003), general health(P = 0.004), social functioning(P = 0.005), role-emotional(P 0.001), and mental health(P 0.001). No significant difference between the two groups regarding vitality was detected(P = 1.000). The LDLT-Rs with BCs had significantly lower scores than LDLT-Rs without BCs in all HRQoL domains(P 0.001) and the mental(P 0.001) and physical(P = 0.0002) component summary scores.CONCLUSION The development of BCs in LDLT-Rs causes a lower range of improvement in HRQoL.     

Listeriosis in infants: Prospective surveillance studies in Canada and Switzerland

ObjectivesInternational data on listeriosis during infancy from large populations are essential to guide evidence-based empiric antibiotic guidelines for sepsis in infancy. We aimed to determine the incidence, clinical manifestations, and outcome of listeriosis in infants <6 months of age in Canada and Switzerland.MethodsProspective, active surveillance of listeriosis in infants <6 months of age was conducted through the Canadian Paediatric Surveillance Program (May 2015 to April 2017) and the Swiss Paediatric Surveillance Unit (April 2017 to March 2018). Confirmed and probable cases were included.ResultsIn Canada, eight sporadic listeriosis cases were reported (incidence, 1.1/100,000 live births/year). In Switzerland, four cases were reported (incidence, 4.5/100,000 live births/year) of which three were part of a confirmed outbreak with an unclear source. In the two countries, eight of the 12 cases (66.6%) presented as early-onset disease (within the first 7 days of life) and none presented after 28 days life.ConclusionsNeonatal listeriosis is rare. Infants presenting with sepsis, especially after 4 weeks of life, may not routinely require empiric antibiotic coverage for listeriosis. Outbreak-related cases still occur. Continued surveillance is important.     

Histopathological changes in the oesophageal mucosa in Egyptian children with corrosive strictures: A single-centre vast experience

BACKGROUND The caustic ingestion continues to be a major problem worldwide especially in developing countries. The long-term complications include stricture and increased life time risk of oesophageal carcinoma. Patients suffered from corrosive induced oesophageal strictures have more than a 1000-fold risk of developing carcinoma of the oesophagus.AIM To determine the possibility of oesophageal mucosal dysplasia after prolonged dilatation in post corrosive stricture.METHODS This observational study was conducted at the Paediatric Endoscopy Unit in Cairo University Children's Hospital. It included children of both sexes older than 2 years of age who had an established diagnosis of post-corrosive oesophageal stricture and repeated endoscopic dilatation sessions for more than 6 mo. All patients were biopsied at the stricture site after 6 mo of endoscopic dilatation. A histopathological examination of an oesophageal mucosal biopsy was performed for the detection of chronic oesophagitis, inflammatory cellular infiltration and dysplasia.RESULTS The mean age of the enrolled children was 5.9 ± 2.6 years; 90% of the patients had ingested an alkaline corrosive substance(potash). The total number of endoscopic dilatation sessions were ranging from 16 to 100 with mean number of sessionswas 37.2 ± 14.9. Histopathological examination of the specimens showed that 85%of patients had evidence of chronic oesophagitis(group A) in the form of basal cell hyperplasia, hyperkeratosis and subepithelial fibrosis. Thirteen percent of the patients had evidence of reactive atypia(group B) in the form of severe neutrophilic intraepithelial inflammatory cellular infiltration, and 2 patients(2%)had mild squamous dysplasia(group C); we rebiopsied these two patients 6 mo after the initial pathological assessment, guided by chromoendoscopy by Lugol's iodine.CONCLUSION The histopathology of oesophageal mucosal biopsies in post-corrosive patients demonstrates evidence of chronic oesophagitis, intraepithelial inflammatory cellular infiltration and dysplasia. Dysplasia is one of the complications of postcorrosive oesophageal stricture.     

Deformation and failure of cartilage in the tensile mode

The aim of this study was to visualize, at the ultrastructural level, the deformation and failure mechanism of cartilage matrix in the tensile mode. Full-thickness dumbbell-shaped specimens were prepared from adult bovines. There were two specimen groups; in the 'parallel' group the specimen axis was parallel to the split lines defining the preferential orientation of the collagen in the articular surface, and in the 'perpendicular' group the specimen axis was perpendicular to the split lines. Specimens were placed with the articular surface uppermost and subjected to a graded series of strain within individual mini-tension devices, while observed with stereomicroscopy and confocal laser scanning microscopy. Thereafter, the changes in the ultrastructure were observed with both scanning and transmission electron microscopy. The mechanism of cartilage failure in the tensile mode comprised the following stages, whether the strain was applied parallel or perpendicular to the split line. (1) At 0% strain a fibrillar meshwork within the articular surface was predominantly orientated in the direction of the split line. (2) As strain increased, the fibrillar meshwork became more orientated in the parallel group and reorientated in the perpendicular group in the direction of the applied strain. (3) After complete reorientation of the fibrillar meshwork in the direction of the applied strain, the initial sign of failure was rupture of the fibrillar meshwork within the articular surface. (4) Subsequently, the rupture rapidly propagated into the deeper layers. Greater strains were required for fibrillar reorientation and complete rupture in the 'perpendicular group' than in the parallel group.