Effectiveness of entomopathogenic nematodes in the control of Cydia pomonella larvae in Northern Italy

Since 2006, a large scale research on the effectiveness of entomopathogenic nematodes (EPN) in the control of codling moth (CM), Cydia pomonella, overwintering larvae has been performed on about 35 ha of pear orchards per year in Emilia-Romagna, Northern Italy. Steinernema carpocapsae and Steinernema feltiae activity was checked after spray applications of EPNs to the trunk and branches. In 2006, the treatment was applied either in spring or in autumn at different doses, before CM pupation; in 2007 the EPN treatment was applied only in autumn at 1.5 x 109 I.J. ha –1. Every year it was distributed by means of a conventional mist blower. The larval mortality was assessed directly on sentinel larvae in card boards on the trunks and indirectly on the eggs laid by the females of the first CM generation in spring. Moreover, each year, a trial was performed applying only S. carpocapsae on sentinel larvae with the aim of testing this nematode at suitable temperatures but at different water volumes. The CM sentinel larvae were effectively parasitized after autumnal EPN application. Moreover, the egg assessment demonstrated a good decrease in CM population in spring 2007, when EPNs had been applied at the best weather conditions (t° 12-14 °C and rain) in the previous autumn

Mutations of penicillin acylase residue B71 extend substrate specificity by decreasing steric constraints for substrate binding

Two mutant forms of penicillin acylase from Escherichia coli strains, selected using directed evolution for the ability to use glutaryl-L-leucine for growth [Forney, Wong and Ferber (1989) Appl. Environ. Microbiol. 55, 2550-2555], are changed within one codon, replacing the B-chain residue Phe(B71) with either Cys or Leu. Increases of up to a factor of ten in k(cat)/K-m values for substrates possessing a phenylacetyl leaving group are consistent with a decrease in K-s. Values of k(cat/)K(m) for glutaryl-L-leucine are increased at least 100-fold. A decrease in k(cat)/K-m for the CySB71 mutant with increased pH is consistent with binding of the uncharged glutaryl group. The mutant proteins are more resistant to urea denaturation monitored by protein fluorescence, to inactivation in the presence of substrate either in the presence of urea or at high pH, and to heat inactivation. The crystal structure of the Leu(B71) mutant protein, solved to 2 X resolution, shows a flip of the side chain of Phe(B256) into the periphery of the catalytic centre, associated with loss of the pi-stacking interactions between Phe(B256) and Phe(B71). Molecular modelling demonstrates that glutaryl-L-leucine may bind with the uncharged glutaryl group in the S-1 subsite of either the wild-type or the Leu(B71) mutant but with greater potential freedom of rotation of the substrate leucine moiety in the complex with the mutant protein. This implies a smaller decrease in the conformational entropy of the substrate on binding to the mutant proteins and consequently greater catalytic activity

Restraining and unleashing chromatin remodelers - structural information guides chromatin plasticity.

Chromatin remodeling enzymes are large molecular machines that guard the genome by reorganizing chromatin structure. They can reposition, space and evict nucleosomes and thus control gene expression, DNA replication and repair. Recent cryo-electron microscopy (cryo-EM) analyses have captured snapshots of various chromatin remodelers as they interact with nucleosomes. In this review, we summarize and discuss the advances made in our understanding of the regulation of chromatin remodelers, the mode of DNA translocation, as well as the influence of associated protein domains and remodeler subunits on the specific functions of chromatin remodeling complexes. The emerging structural information will help our understanding of disease mechanisms and guide our knowledge toward innovative therapeutic interventions. Copyright © 2020 Elsevier Ltd. All rights reserved

Influence of Portosystemic Shunt on Liver Regeneration after Hepatic Resection in Pigs

Objective. The minimal amount of liver mass necessary for regeneration is still a matter of debate. The aim of the study was to analyze liver regeneration factors after extended resection with or without portosystemic shunt. Methods. An extended left hemihepatectomy was performed in 25 domestic pigs, in 15 cases after a portosystemic H-shunt. The expression of Ki-67, VEGF, TGF-α, FGF, and CK-7 was analyzed in paraffin-embedded tissue sections. Results. The volume of the remnant liver increased about 2.5-fold at the end of the first week after resection. With 19 cells/10 Glisson fields versus 4/10, Ki-67-expression was significantly higher in the H-shunt group. VEGF- and CK-7-expressions were significantly higher in the control group. No significant change was found in FGF-expression. The expression of TGF-α was higher, but not significantly, in the control group. Conclusions. The expression of Ki-67, and therefore hepatocyte regeneration, was increased in the shunt group. The expression of CK-7 on biliary epithelium and the expression of VEGF, however, were stronger in the control group

Impact of response evaluation for resectable esophageal adenocarcinoma – A retrospective cohort study

AbstractIntroduction: The standard treatment concept in patients with locally advanced adenocarcinoma of the esophagogastric junction is neoadjuvant chemotherapy, followed by tumor resection in curative intent. Response evaluation of neoadjuvant chemotherapy using histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer. Methods: We assessed the impact of the various methods of response control and their value in correlation to established prognostic factors in a cohort of patients with adenocarcinoma at the gastroesophageal junction treated by neoadjuvant chemotherapy. Results: After neoadjuvant chemotherapy, in 56 consecutive patients with locally advanced (T2/3/4 and/or N0/N1) esophageal adenocarcinoma an oncologic tumor resection for curative intent was performed. Median follow-up was 44 months. Histopathological tumor stages were stage 0 in 10.7%, stage I in 17.9%, stage II in 21.4%, stage III in 41.1% and stage IV 8.9%. The 3-year overall survival (OS) rate was 30.3%. In univariate analysis, ypN-status, histopathological tumor stage and tumor regression grade correlated significantly with overall survival (p = 0.022, p = 0.001, p = 0.035 respectively). Clinical response evaluation could not predict response and overall survival (p = 0.556, p = 0.254 respectively). Conclusion: After preoperative chemotherapy, outcomes of esophageal carcinoma are best predicted utilizing pathological tumor stage and histologic tumor regression. Clinical response assessments were not useful for guidance of treatment

Sequencing of folding events in Go-like proteins

We have studied folding mechanisms of three small globular proteins: crambin (CRN), chymotrypsin inhibitor 2 (CI2) and the fyn Src Homology 3 domain (SH3) which are modelled by a Go-like Hamiltonian with the Lennard-Jones interactions. It is shown that folding is dominated by a well-defined sequencing of events as determined by establishment of particular contacts. The order of events depends primarily on the geometry of the native state. Variations in temperature, coupling strengths and viscosity affect the sequencing scenarios to a rather small extent. The sequencing is strongly correlated with the distance of the contacting aminoacids along the sequence. Thus $\alpha$-helices get established first. Crambin is found to behave like a single-route folder, whereas in CI2 and SH3 the folding trajectories are more diversified. The folding scenarios for CI2 and SH3 are consistent with experimental studies of their transition states.Comment: REVTeX, 12 pages, 11 EPS figures, J. Chem. Phys (in press

Proximal Femoral Nail Unlocked versus Locked (ProFNUL): a protocol for a multicentre, parallel-armed randomised controlled trial for the effect of femoral nail mode of lag screw locking and screw configuration in the treatment of intertrochanteric femur fractures

Introduction: Intertrochanteric fractures are common fragility injuries in the elderly. Surgical fixation using intramedullary devices are one of the widely used management options. To date, evidence demonstrating the effects of lag screw configuration and the mode of lag screw locking in these devices is lacking. The purpose of this study is to investigate whether the lag screw configuration (single vs integrated dual interlocking screw) and the mode of lag screw locking (static vs dynamic) of a femoral nail device result in differences in clinical and functional outcomes. Methods and Analysis: A multicentre, pragmatic, single-blinded randomised controlled trial (RCT) with a three-arm parallel group design is proposed. Nine-hundred patients with intertrochanteric fractures (A1 and A2 AO/OTA) will be randomised to fracture treatment using a Gamma3 nail (Stryker; proximally dynamic) or a Trigen Intertan nail (Smith & Nephew) in a dynamic or static lag screw configuration. The primary outcome measure consists of radiological evidence of construct failure within 6 months following surgery, with failure being defined as breakage of the femoral nail or distal locking screw, a change in tip-apex distance of more than 10 mm or lag screw cut-out through the femoral head. Secondary outcomes include surgical data (operation time, fluoroscopy time), complications (surgical site infection, reoperation, patient death), return to mobility and home circumstances, functional independence, function and pain. Patients who are able to walk independently with or without a mobility aid and are able to answer simple questions and follow instructions will be asked to participate in three dimensional gait analysis at 6 weeks and 6 months to assess hip biomechanics from this cohort. Additional secondary measures of gait speed, hip range of motion, joint contact and muscle forces and gross activity monitoring patterns will be obtained in this subgroup. Ethics and Dissemination: The Central Adelaide Local Health Network Human Research Ethics Committee has approved the protocol for this RCT (HREC/17/RAH/433). The results will be disseminated via peer-reviewed publications and presentations at relevant conferences.Arjun Sivakumar, Dominic Thewlis, Andreas Ladurner, Suzanne Edwards, Mark Rickma

Natural history, clinical pattern, and surgical considerations of pneumatosis intestinalis

<p>Abstract</p> <p>Objective</p> <p>Pneumatosis intestinalis has been increasingly detected in recent years with the more frequent use of computed tomography for abdominal imaging of the intestine. The underlying causes of the gas found during radiographic studies of the bowel wall can vary widely and different hypotheses regarding its pathophysiology have been postulated. Pneumatosis intestinalis often represents a benign condition and should not be considered an argument for surgery. However, it can also require life-threatening surgery in some cases, and this can be a difficult decision in some patients.</p> <p>Methods</p> <p>The spectrum of pneumatosis intestinalis is discussed here based on various computed tomographic and surgical findings in patients who presented at our University Medical Centre in 2003-2008. We have also systematically reviewed the literature to establish the current understanding of its aetiology and pathophysiology, and the possible clinical conditions associated with pneumatosis intestinalis and their management.</p> <p>Results</p> <p>Pneumatosis intestinalis is a primary radiographic finding. After its diagnosis, its specific pathogenesis should be ascertained because the appropriate therapy is related to the underlying cause of pneumatosis intestinalis, and this is sometimes difficult to define. Surgical treatment should be considered urgent in symptomatic patients presenting with an acute abdomen, signs of ischemia, or bowel obstruction. In asymptomatic patients with otherwise inconspicuous findings, the underlying disease should be treated first, rather than urgent exploratory surgery considered. Extensive and comprehensive information on the pathophysiology and clinical findings of pneumatosis intestinalis is provided here and is incorporated into a treatment algorithm.</p> <p>Conclusions</p> <p>The information presented here allows a better understanding of the radiographic diagnosis and underlying aetiology of pneumatosis intestinalis, and may facilitate the decision-making process in this context, thus providing fast and adequate therapy to particular patients.</p

Higher body mass index is associated with larger postoperative improvement in patient-reported outcomes following total knee arthroplasty

BackgroundTotal knee arthroplasty is known to successfully alleviate pain and improve function in endstage knee osteoarthritis. However, there is some controversy with regard to the influence of obesity on clinical benefits after TKA. The aim of this study was to investigate the impact of body mass index (BMI) on improvement in pain, function and general health status following total knee arthroplasty (TKA).MethodsA single-centre retrospective analysis of primary TKAs performed between 2006 and 2016 was performed. Data were collected preoperatively and 12-month postoperatively using WOMAC score and EQ-5D. Longitudinal score change was compared across the BMI categories identified by the World Health Organization.ResultsData from 1565 patients [mean age 69.1, 62.2% women] were accessed. Weight distribution was: 21.2% BMI < 25.0 kg/m2, 36.9% BMI 25.0–29.9 kg/m2, 27.0% BMI 30.0–34.9 kg/m2, 10.2% BMI 35.0–39.9 kg/m2, and 4.6% BMI ≥ 40.0 kg/m2. All outcome measures improved between preoperative and 12-month follow-up (p < 0.001). In pairwise comparisons against normal weight patients, patients with class I-II obesity showed larger improvement on the WOMAC function and total score. For WOMAC pain improvements were larger for all three obesity classes.ConclusionsPost-operative improvement in joint-specific outcomes was larger in obese patients compared to normal weight patients. These findings suggest that obese patients may have the greatest benefits from TKA with regard to function and pain relief one year post-op. Well balanced treatment decisions should fully account for both: Higher benefits in terms of pain relief and function as well as increased potential risks and complications.Trial registrationThis trial has been registered with the ethics committee of Eastern Switzerland (EKOS; Project-ID: EKOS 2020–00,879