Incorporation of a molybdenum atom in a Rubredoxin-type Centre of a de novo-designed α3DIV-L21C three-helical bundle peptide

PB would thank the PTNMRPhD (PD/00065/2013). VLP thanks the NIH for support (GM141086).The rational design and functionalization of small, simple, and stable peptides scaffolds is an attractive avenue to mimic catalytic metal-centres of complex proteins, relevant for the design of metalloenzymes with environmental, biotechnological and health impacts. The de novo designed α3DIV-L21C framework has a rubredoxin-like metal binding site and was used in this work to incorporate a Mo-atom. Thermostability studies using differential scanning calorimetry showed an increase of 4 °C in the melting temperature of the Mo-α3DIV-L21C when compared to the apo-α3DIV-L21C. Circular dichroism in the visible and far-UV regions corroborated these results showing that Mo incorporation provides stability to the peptide even though there were almost no differences observed in the secondary structure. A formal reduction potential of ∼ −408 mV vs. NHE, pH 7.6 was determined. Combining electrochemical results, EPR and UV–visible data we discuss the oxidation state of the molybdenum centre in Mo-α3DIV-L21C and propose that is mainly in a Mo (VI) oxidation state.publishersversionpublishe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Single versus two-operator endoscopic biliary cannulation technique: a multicenter matched-case analysis and a literature review

BACKGROUND: The aim of this study was to compare the outcomes of physician-controlled, using both long and short endoscopic-retrograde-cholangiopancreatography wire systems, and assistant-controlled guide-wire biliary cannulation techniques, and to perform a literature review on this topic. METHODS: The endoscopic databases of three Endoscopic Centers were reviewed to identify all consecutive patients with an intact papilla who, between July 2013 and December 2014, underwent an endoscopic-retrograde-cholangiopancreatography. A total of 240 patients (80 for each group) were matched 1:1, by gender, age and indications for procedure and were included in the analysis. All articles of physician-controlled vs. assistant-controlled guide-wire biliary cannulation techniques, were extracted up to December 2016, and included in the review. RESULTS: There were no statistically significant differences in primary and final (using rescue technique) cannulation rate between the three groups. The mean primary cannulation time and overall cannulation time were shorter in the two groups of physician-controlled guide-wire compared to the assistant-controlled guide-wire group, but the difference was not statistically significant. The total procedure time did not differ significantly between the 3 groups, but the physician-controlled guide-wire using short wire system was associated with a trend toward a shorter time compared to the other two techniques. There were no statistically significant differences in complication rates between the three groups. Three pertinent articles were included in the review. The mean procedure success and complication rates were 92% and 7%, respectively. CONCLUSIONS: The literature review and our results shows that all these techniques have equally efficacy and safety for guide-wire cannulation

Synthesis and styrene copolymerization of novel ring-substituted isobutyl phenylcyanoacrylates

Novel ring-substituted isobutyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2CH(CH3)2 , where R is 2-ethyl, 4-(4-bromophenoxy), 2-(4-chlorophenoxy), 2-(4-fluorophenoxy), 4-(4-methoxyphenoxy), 3-(4-methylphenyl), 4-(4-methylphenyl), 4-acetoxy, 2,5-dimethyl were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and isobutyl cyanoacetate and characterized by CHN analysis, IR, 1H and 13C NMR. The acrylates were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis

Chromatin-Bound IkBa Regulates a Subset of Polycomb Target Genes in Differentiation and Cancer

IkB proteins are the primary inhibitors of NF-kB. Here, we demonstrate that sumoylated and phosphorylated IkBa accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IkBa modulates Polycomb recruitment and imparts their competence to be activated by TNFa. Mutations in the Drosophila IkBa gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-kB. Oncogenic transformation of keratinocytes results in cytoplasmic IkBa translocation associated with a massive activation of Hox. Accumulation of cytoplasmic IkBa was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation

Chromatin-bound IκB-alpha regulates a subset of polycomb target genes in differentiation and cancer

IκB proteins are the primary inhibitors of NF-κB. Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IκBα modulates Polycomb recruitment and imparts their competence to be activated by TNF-alpha. Mutations in the Drosophila IκBα gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-κB. Oncogenic transformation of keratinocytes results in cytoplasmic IκBα translocation associated with a massive activation of Hox. Accumulation of cytoplasmic IκBα was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys