INTRODUCTION We present the results on retrospective analysis about the efficacy of Certolizumab Pegol (CZP), an anti-tumor necrosis factor-alpha agent, as monotherapy on skin psoriasis (PsO) in patients affect both by psoriatic arthritis (PsA) and mild-severe PsO. To date, the CZP is authorized for the treatment of PsA beyond that rheumatoid arthritis, axial spondyloarthritis/ankylosing spondylitis, and Crohn’s disease but still not for PsO. METHODS Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI). Twelve patients (9M and 3F mean age 57.8±8 years) were enrolled in our study. Nine patients had been previously treated with others biologic agents, three patients were naïve. Clinical and laboratory evaluations including Psoriasis area and Severity Index (PASI), erythrosedimentation rate (ESR) and C-reactive Protein (CRP) were performed at baseline (BL), at week 12 (W12), week 24 (W24) and week 52 (W52) of treatment. Although combination between Methotrexate and CZP is allowed, wffective option in the treatment of cutaneous symptoms of PsO. Limitations of our study are represented by the relatively short observation time (W52) and by numeric small study group. Long-term data with a larger number of enrolled patients are necessary in order to confirm our preliminary observations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Green and sustainable synthesis of chemicals from renewable feedstocks via biotransformation approach has gained an increasing attention in the recent years. In this report, we aimed to develop enzymatic cascades to efficiently convert L-phenylalanine (L-Phe) into 2-phenylethanol (2-PE) and phenylacetic acid (PAA), L-tyrosine (L-Tyr) into tyrosol (p-hydroxyphenylethanol, p-HPE) and p-hydroxyphenylacetic acid (p-HPAA). The enzymatic cascade was casted into aromatic aldehyde formation module, followed by aldehyde reduction module, or aldehyde oxidation module, to achieve one-pot biotransformation using the recombinant Escherichia coli. Biotransformation of 50 mM L-Phe yielded PAA of 6.76 g/L with more than 99% conversion and 2-PE of 5.95 g/L with 97% conversion. And the bioconversion efficiency of p-HPAA and p-HPE from L-Tyr reached up to 88% and 94%, respectively. In addition, m-fluoro-phenylalanine was further employed as a non-natural aromatic amino acid substrate to obtain m-fluoro-phenylacetic acid, and above 96% conversion was achieved. In conclusion, our results demonstrated high-yielding and potential industrial synthesis of above aromatic compounds by one-pot cascade biocatalysis. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This study examined the multidimensional nature of experiences of being an intimate partner of an Australian veteran or emergency service first responder (ESFR) with posttraumatic stress disorder (PTSD). Using a qualitative phenomenological approach, inductive thematic analysis was undertaken on data collected in 2017-2018 through individual interviews with a purposive sample of 22 partners of veterans, paramedics, fire and police officers living in Australia. Analysis revealed that the key concern of the participants was to protect their family unit and the intimate relationship, highlighting the ways in which they adapted, managed and coped with the changes that PTSD brought to the relationship. However, lack of understanding by healthcare providers, government, military and emergency service organizations of their daily lives, and of the strength of commitment to their relationship, resulted in a sense of invisibility and was revealed as the key barrier to the support they crave. The findings underscore the importance of recognizing the significance of the intimate relationship in trauma recovery and of responding to the support needs of the intimate partner. © 2020 John Wiley & Sons Ltd.Common ragweed (Ambrosia artemisiifolia) is a notorious invasive weed that has spread across most temperate regions of the world. The beetle (Ophraella communa) is considered to be an effective control agent against A. artemisiifolia. As an oligophagous insect, its olfactory system is extremely important for host seeking in the wild. To the best of our knowledge, there is no report on the molecular mechanisms underlying olfaction recognition in this beetle. Hence, in this study, we characterized the odorant receptor co-receptor of O. communa and named it as 'OcomORco’. Real-time quantitative PCR (qRT-PCR) showed that, compared to the control treatment, RNA interference (RNAi) strongly reduced the expression of OcomORco by 89% in male and 90% in female beetles. Electroantennogram assay showed that the antennal response of both male and female beetles to four volatiles of A. artemisiifolia was significantly reduced. The injected male or female beetles lost their preference for plant leaves as observed in the behavioural tests. In addition, disruption of the expression of OcomORco resulted in a reduction of oviposition, while there was no difference in larval hatching rate between control and knockdown females. We demonstrated that OcomORco plays a vital role in olfactory perception and host search in O. communa, and it is involved in oviposition in an indirect way. © 2020 The Royal Entomological Society.Application of new strategies for supramolecular self-assembly can significantly impact the properties and/or functions of supramolecular polymers. In order to realize a facial strategy for the development of solvent-free supramolecular polymers in bulk, „deep eutectic solvents” were employed. Cyclodextrins and natural acids were used to prepare deep eutectic supramolecular polymers (DESPs). Deep eutectic solvents have special characteristics that endow DESPs with unique macroscopic properties and excellent processability. DESPs exhibit supramolecular adhesion and temperature-dependent behavior originated from the combined effects of deep eutectic solvents and supramolecular polymerization. Because DESPs are solvent-free and display interesting macroscopic properties, they have potential as new adaptive materials. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIMS To assess efficacy and safety of 26-week treatment with insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi) compared with insulin glargine U100 (iGlar) in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs). MATERIALS AND METHODS This phase 3, multicenter, open label, 11 randomized, parallel-group study compared efficacy of iGlarLixi and iGlar in patients with T2DM, HbA1c of ≥7.5% to ≤9.5% and fasting plasma glucose ≤10.0 mmol/L (180 mg/dL). The primary endpoint was change in HbA1c from baseline to week 26. RESULTS Patients were randomized to iGlarLixi (n = 260) or iGlar (n = 261) (mean age 59.7 years, baseline BMI 26.04 kg/m2 , and HbA1c 8.04% [64.4 mmol/mol]). HbA1c reduction was significantly greater with iGlarLixi (-1.40% [-15.3 mmol/mol]) than with iGlar (-0.76% [-8.3 mmol/mol]). Significantly more iGlarLixi patients reached HbA1c less then 7% at week 26 (71.5% vs. 38.5%, P  less then  0.0001), with significantly lower weight gain (LS mean difference - 1.06 kg, P  less then  0.0001). Documented symptomatic hypoglycemia (plasma glucose ≤3.9 mmol/L [70 mg/dL]) was recorded in 14.2% of patients with iGlarLixi and 12.3% with iGlar. No severe hypoglycemia was reported in either group. Other than the expected gastrointestinal issues associated with glucagon-like peptide 1 receptor agonists, we found no major difference in the incidence of TEAEs. CONCLUSIONS HbA1c reduction was significantly greater with iGlarLixi than with iGlar; significantly more patients achieved HbA1c less then 7%, with no additional risk of hypoglycemia and without weight gain. iGlarLixi (11) provided an effective treatment option for Japanese patients with T2DM inadequately controlled on OADs. Clinical Trial Number NCT02752828. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Lipid droplets (LDs) serve as one of the major reservoirs in conidia of Magnaporthe oryzae and are quickly utilized during appressorium formation. Here, we identified a gene, LDP1, encoding a perilipin that is important for LD formation and utilization during appressorium maturation. LDP1 is highly expressed in conidium and immature appressorium. Disruption mutants of LDP1 were significantly reduced in virulence, due to appressorial turgor reduction and difficulty in penetration. LDs were significantly reduced in the Δldp1 mutant, indicating LDP1 was required for LDs formation. LDP1 was colocalized with the LDs in conidium and immature appressorium but was gradually separated during appressorium maturation. A typical intracellular triacylglycerol lipase, TGL1-2, was clearly separated with LDs in conidium and immature appressorium but was well colocalized with LDs during appressorium maturation. The subcellular localization of TGL1-2 was affected by LDP1. These data suggested that LDP1 was bound to LDs for protecting from utilization in conidia and at the early appressorium stage but was separated from LDs for lipase entering and degradation. LDP1 was phosphorylated by CPKA at Thr96, which was essential for its localization and functions. These data indicate perilipin LDP1 can coordinate LD formation and utilization for appressorium-mediated infection of M. oryzae. © 2020 Society for Applied Microbiology and John Wiley & Sons Ltd.Several types of human papillomaviruses induce warts. Warts are one of the most common infections in childhood with a reported prevalence of up to 20%. Warts are divided clinically into genital and nongenital forms. Plantar warts are common nongenital warts. In this series, five pediatric cases treated with CO2 laser for their plantar warts are presented. One patient was a known case of Hodgkin’s lymphoma. Three of our patients had history of unsuccessful treatments with other modalities, while the other had received no previous treatment. CO2 laser with continuous mode (focused and defocused) was used. In our cases, only one session was enough for clearance of the warts. All the patients were visited 1 week and 3 months after treatment to assess the efficacy and any possible recurrences. Follow-up showed that all the patients remained in remission up to 3 months posttreatment with no adverse events. © 2020 Wiley Periodicals LLC.Quality report cards addressing information asymmetry in the health care market have become a popular strategy used by policymakers to improve the quality of care for older people. Using individual level data from the largest German sickness fund merged with institutional level data, we examine the relationship between reported nursing home quality, as measured by recently introduced report cards, nursing home prices, nursing home’s location, and the individual choice of nursing homes. Report cards were stepwise introduced as of 2009, and we use a sample of 2010 that includes both homes that had been evaluated at that time and that had not yet been. Thus, we can distinguish between institutions with above and below average ratings as well as nonrated nursing homes. We find that the probability of choosing a nursing home decreases in distance and price. However, we find no economically significant effect of reported quality on individuals’ choice of nursing homes. © 2020 John Wiley & Sons, Ltd.In Saccharomyces cerevisiae, vacuolar H+ -ATPase (V-ATPase) involved in the regulation of intracellular pH homeostasis has been shown to be important for tolerances to cadmium, cobalt, and nickel. However, molecular mechanism underlying the protective role of V-ATPase against these metals remains unclear. In this study, we show that cadmium, cobalt, and nickel disturbed intracellular pH balance by triggering cytosolic acidification and vacuolar alkalinization, likely via their membrane permeabilizing effects. Since V-ATPase plays a crucial role in pumping excessive cytosolic protons into the vacuole, the metal-sensitive phenotypes of the Δvma2 and Δvma3 mutants lacking V-ATPase activity were supposed to result from highly acidified cytosol. However, we found that the metal-sensitive phenotypes of these mutants were caused by increased production of reactive oxygen species, likely as a result of decreased expression and activities of manganese superoxide dismutase and catalase. In addition, the loss of V-ATPase function led to aberrant vacuolar morphology and defective endocytic trafficking. Furthermore, the sensitivities of the Δvma mutants to other chemical compounds (i.e., acetic acid, H2 O2 , menadione, tunicamycin, and cycloheximide) were a consequence of increased endogenous oxidative stress. These findings therefore suggest the important role of V-ATPase in preventing endogenous oxidative stress induced by metals and other chemical compounds. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND/OBJECTIVE Before approval of andexanet alfa, off-label treatment with 4-factor prothrombin complex concentrate (4F-PCC) was often utilized for the management of life-threatening hemorrhages associated with oral factor-Xa inhibitors. We evaluated the operational processes and outcomes of patients with oral factor Xa inhibitor-associated intracranial hemorrhages (ICH) treated with andexanet alfa or 4F-PCC. METHODS We performed a retrospective, single-center case series of rivaroxaban or apixaban-associated ICH between 2016-2019 treated with andexanet alfa or 4F-PCC. Good or excellent hemostatic effectiveness, good functional outcome [Glasgow Outcome Scores (GOS) > 3] at hospital discharge, and incidence of thrombosis within 30-days were reported. RESULTS Eighteen patients were included in the andexanet alfa cohort and 11 in the 4F-PCC cohort. Excellent or good hemostasis occurred in 88.9% of andexanet alfa-treated patients and 60% of 4F-PCC-treated patients. Good functional outcome on discharge occurred in 55.6% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Thrombotic complications occurred in 16.7% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Median order-to-administration time was 1.1 hours [0.8-1.4] vs. 0.5 hours [0.1-0.8] in the andexanet alfa and 4F-PCC group, respectively. The median cost of therapy was $29,970/patient vs. $6,925/patient in the andexanet alfa and 4F-PCC group, respectively. CONCLUSIONS We observed higher rates of occurrence of good or excellent hemostasis and GOS >3 on hospital discharge and increased incidence of thrombosis in patients who received andexanet alfa compared to 4F-PCC for oral factor Xa inhibitor reversal. However, patients receiving 4F-PCC had lower pre-reversal GCS and larger pre-reversal ICH volume. This article is protected by copyright. All rights reserved.BACKGROUND Neonatal management of patients with hypoplastic left heart syndrome and -complex remains a challenging task. Whereby the „hybrid” palliation is often reserved for high-risk patients as a „rescue” procedure. AIM This study documents the anaesthetic challenges and potential complications associated with the Giessen hybrid stage I approach. METHODS The Giessen hybrid stage I approach is focused on surgical bilateral pulmonary artery banding. Retrospective perioperative data were analysed. Contrary to a stable group A, inotropic treatment before surgery for treatment of postnatal shock classified patients as unstable (Group B). Clinical Outcomes considered were in-hospital mortality, duration of postoperative mechanical ventilation, postoperative time at the intensive care unit, perioperative vasoactive medication requirements, and red blood cell transfusion. RESULTS From June 1998 to December 2015, 185 patients were allocated to Group A (n=165) and Group B (n=20). The in-hospital mortality was 2.2% with no difference between the groups. There was also no difference in the postoperative time on mechanical ventilation and the time in the intensive care unit. Vasoactive medication was more often required in Group B (100 %) compared to Group A (19 %). In Group B more red blood cells were transfused 6.0 ± 8.3 vs. 2.0 ± 5.8 ml * kg-1 in Group A (p less then 0.05, 95% CI 0,0 – 2,6). CONCLUSION Considering a learning curve, anaesthesia for surgical bilateral pulmonary artery banding palliating patients with hypoplastic left heart syndrome and -complex can safely be performed, independent from the preoperative clinical status. This article is protected by copyright. All rights reserved.African Americans (AA), the second largest racial/ethnic minority group in the United States (US), carry the largest mortality burden of cancer compared with other racial/ethnic groups (Cancer Facts & Figures for African Americans, 2019-2021, American Cancer Society).One solution to address this disparity is through cancer-related genetic counseling and testing (CGT). Although CGT is utilized among the general population, it remains underutilized among AA populations. Community-engaged and community-driven health promotion programs within faith-based organizations (FBOs) have been successfully implemented and delivered among AA populations (Israel et al., American Journal of Public Health, 100, 2010, 2094). FBOs are well positioned for cancer-related health promotion and equipped as conduits of health education and information distribution for cancer prevention. In the present pilot study, a community-based participatory approach (CBPR) was used to collect exploratory data on attitudes, perceptions, and beliens for genetic counselors, medical providers, and health promotion personnel as to how AA faith populations view CGT and the utility of FBOs as promoters of CGT information. © 2020 National Society of Genetic Counselors.The first example of asymmetric Guerbet reaction has been developed. Using commercially available, classic Noyori Ru(II)-diamine-diphosphine catalysts, well-known in asymmetric hydrogenation, racemic secondary alcohols are shown to couple with primary alcohols in the presence of a base, affording new chiral alcohols with enantiomeric ratios of up to 991. Requiring no reducing agents, the protocol provides an easy, alternative route for the synthesis of chiral alcohols. Mechanistic studies reveal that the reaction proceeds via a Ru-catalyzed asymmetric hydrogen-autotransfer process in concert with a base-promoted allylic alcohol isomerization. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.In this comment on the Essay entitled „Bad Language” by Dunitz I add new elements which enlighten the discussion. I hope that they contribute to suppress ambiguities and preconceived ideas about chirality. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.IDM-1 is a new silica zeolite with an ordered and well-defined framework constructed by alternating pentasil layers and interrupted layers, giving rise to an intersecting system of straight medium pores and undulating extra-large lobed pores. This unique structure was solved by rotation electron diffraction and refined against synchrotron powder X-ray diffraction data. Despite the presence of both Si(OSi)3(OH) and Si(OSi)2(OH)2 sites, this new zeolite presents high thermal stability, withstanding calcination even to 1000ºC. The location of defects at specific sites of the structure results in alternating hydrophobic SiO2 and hydrophilic SiO(2-x)(OH)2x intracrystalline regions. This peculiar combination of intersecting medium and extra-large pores and alternating regions of different chemical character may provide this zeolite with unique catalytic properties. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.In this series of articles, the board members of ChemSusChem discuss recent research articles that they consider of exceptional quality and importance for sustainability. This entry features Prof. R. C. Sun, who highlights the fabrication of lignin nanoparticles and their application in composites, suggesting that further studies and discoveries of the structures and inherent properties of lignin will contribute to extensive and standardized applications of this new green nanomaterial. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.We investigated whether sex differences exist in cyclooxygenase-dependent effects on membrane potential and relaxation in mice mesenteric resistance arteries. Mesenteric small arteries of 9-12-week-old, male and female, wild-type mice, db/+ mice and diabetic db/db mice were mounted in myographs for measurements of isobaric diameter and smooth muscle cell membrane potential. Acetylcholine caused smaller dilation of arteries from male db/+ mice compared to arteries from female db/+ mice. In the presence of the NO-synthase inhibitor Nω -nitro-L-arginine methyl ester (L-NAME), acetylcholine induced dilation of arteries from males increased in the presence of indomethacin and the COX-1 specific inhibitor FR122047. The presence of indomethacin was also associated with a more negative membrane potential in arteries from males. In arteries from db/db mice, no sex differences were seen. In arteries from male but not female wild-type mice, the thromboxane receptor blocker SQ29,548 increased relaxation to acetylcholine. In contrast to arteries from female mice, COX (most likely COX-1)-derived prostanoids and activation of thromboxane receptors counteract acetylcholine vasodilatation probably through increased smooth muscle depolarization in arteries from male mice. In mice with diabetes and pronounced endothelial dysfunction, inhibition of COX did not enhance acetylcholine vasodilatation. This article is protected by copyright. All rights reserved.Microorganisms attached to particles have been shown to be different from free-living microbes and to display diverse metabolic activities. However, little is known about the ecotypes associated to particles and their substrate preference in anoxic marine waters. Here, we investigate the microbial community colonizing particles in the anoxic and sulfide-rich waters of the Black Sea. We incubated beads coated with different substrates in situ at 1,000 and 2,000 m depth. After 6 h, the particle-attached microbes were dominated by Gamma- and Alphaproteobacteria, and groups related to the phyla Latescibacteria, Bacteroidetes, Planctomycetes and Firmicutes, with substantial variation across the bead types, indicating that the attaching communities were selected by substrate. Further laboratory incubations for 7 days suggested the presence of a community of highly specialized taxa. After incubation for 35 days, the microbial composition across all beads and depths was similar and primarily composed of putative sulfur cycling microbes. In addition to the major shared microbial groups, subdominant taxa on chitin and protein-coated beads were detected pointing to specialized microbial degraders. These results highlight the role of particles as sites for attachment and biofilm formation, while the composition of organic matter defined a secondary part of the microbial community. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.As the market for personalized lung cancer medicine expands, demand for molecular diagnostic tools in general, and methods of detecting multiple genes with qualitative, quantitative, and high specificity in particular, have grown. Here, we propose a system for the effective detection of lung cancer-specific, long-length epidermal growth factor receptor (EGFR) gene mutations using a topological transformation nanobarcoding technique (TNT). In former TNT studies, EGFR was successfully detected in cell environments and at test stages in the presence of a reference gene. However, because typical EGFR target concentrations are significantly lower at the clinical stage and the probe-binding ability of long-length targets is lower that of short targets, our system employs polymerase chain reaction (PCR) amplification, restriction, and filtering (PRF) for EGFR fragmentation to maximize performance. In a PRF system, the target is amplified by PCR, cut to a suitable size by a restriction enzyme, and filtered by a magnetic bead. With detection limits of 0.3555% and 1.500% for EGFR Del 19 and L858R mutations, respectively, the proposed TNT with PRF can effectively distinguish mutant cell lines and efficiently detect various lengths of genetic variations in clinical trials. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.INTRODUCTION The analysis of plant and herbal samples is a challenging task for analytical chemists due to the complexity of the matrix combined with the low concentration of analytes. In recent years different liquid-phase microextraction (LPME) techniques coupled with a variety of analytical equipment have been developed for the determination of both organic and inorganic analytes. OBJECTIVE Over the past few years, the number of research papers in this field has shown a markedly growing tendency. Therefore, the purpose of this review paper is to summarise and critically evaluate research articles focused on the application of LPME techniques for the analysis of plant and herbal samples. RESULTS Due to the complex nature of the samples, the direct application of LPME techniques to the analysis of plants has not often been done. LPME techniques as well as their modalities have been commonly applied in combination with other pretreatment techniques, including a solid-liquid extraction technique supported by mechanical agitation or auxiliary energies for plant analysis. Applications and the most important parameters are summarised in the tables. CONCLUSION This review summarises the application of the LPME procedure and shows the major benefits of LPME, such as the low volume of solvents used, high enrichment factor, simplicity of operation and wide selection of applicable detection techniques. We can expect further development of microextraction analytical methods that focus on direct sample analysis with the application of green extraction solvents while fully automating procedures for the analysis of plant materials. © 2020 John Wiley & Sons, Ltd.BACKGROUND The 5-factor modified frailty index(mFI-5) is a new, NSQIP-based, predictive tool for mortality and postoperative complications. The mFI-5’s predictive ability has been validated within the large-scale NSQIP database but applicability in institutional databases has not been investigated. We sought to assess the association between the mFI-5 and morbidity/mortality at the institutional level. METHODS A divisional database was queried for 2017 elective colorectal resections and an mFI-5 calculated. The main outcome measure was the association and predictive value of the mFI-5 with major morbidity/mortality and minor complications. Univariable analyses were performed via the Cochran-Armitage Test and Cramer’s V. Logistic regression evaluated the relationship between the mFI-5 and morbidity/mortality while accounting for demographics and pre-operative risk factors. ROC curves were plotted to visualize the predictive strength for outcomes. RESULTS 412 patients were analyzed. 8.7% had major morbidity/mortality and 31.6% minor complications. The mFI-5 categorized patients into 0(n=335), 1(n=58), and 2+(n=19) groups. Univariable analysis showed a higher mFI-5 was associated significantly with major morbidity/mortality(p=0.004), but not minor(p=0.281). Multivariable logistic regression showed a strong association between an mFI-5 score of 2+ with major complications (Major OR=4.616, CI(1.442-14.776), p=0.010). ROC Curves showed the mFI-5 was poor for predicting outcomes and performed better when other risk factors were added to the model. CONCLUSION The mFI-5 tool has an independent association with major morbidity/mortality in an institutional dataset for elective colorectal surgery, but is not predictive. Its predictive ability is enhanced when other patient-specific risk factors are incorporated. This article is protected by copyright. All rights reserved.Modular organization provides flexibility for colonial animals to deal with variable and unpredictable environmental conditions since each module has specific tasks within the colony, such as feeding, defending or reproducing. Depending on the selecting pressures, sessile organisms may phenotypically adjust the morphology of each module or modify their density, increasing individual fitness. Here we used the marine bryozoan Schizoporella errata (Cheilostomata, Schizoporellidae) to test how the divergent conditions between two artificial habitats, the location inside a marina (IM) and the external wall of the breakwater (BW), affect colony size and the density of the distinct modules. The density of avicularia and ovicells, modules related to defense and reproduction, respectively, did not differ between habitats. However, colonies growing in the turbulent waters of BW were, in general, larger and had higher density of feeding autozooids than those at IM. Reciprocal transplants of bryozoan clones indicated that trait variation is genotype-dependent but varies according to the environmental conditions at the assigned location. The occurrence of larger colonies with more zooids in BW is probably linked to the easier feeding opportunity offered by the small diffusive boundary layer around the colony at this location. Since in colonial polymorphic organisms each module (zooid) performs a specific function, the phenotypic response is not uniform across colonies, affecting only those modules that are susceptible to variations in the main selective pressures. Understanding the importance of colony-level plasticity is relevant to predict how modularity will contribute to organisms to deal with human-induced environmental changes in coastal habitats. © 2020 Wiley Periodicals, Inc.I wrote this as a narrative piece for school, but it is a very honest description of how I’m feeling at this time. I just wanted to reassure people that I am ok. For anyone else who is feeling the same as I am, it’s ok. I think it is good for us to be honest about how we are feeling, and it is perfectly reasonable for us to feel confusion during this time. I also think it is good for us to not let any anxiety overwhelm us. So let it out. Talk to someone. Write it down. And breathe. For me, watching the sunrise this morning was a good way to focus on something other than the chaos, other than my feelings. © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).Understanding the catalysis of oxidative reactions by TAML activators of peroxides, i. e. iron(III) complexes of tetraamide macrocyclic ligands, advocated a spectrophotometric procedure for quantifying the catalytic activity of TAMLs for colorless targets (kII ’, M-1  s-1 ), which is incomparably more advantageous in terms of time, cost, energy, and ecology than NMR, HPLC, UPLC, GC-MS and other similar techniques. Dyes Orange II or Safranin O (S) are catalytically bleached by non-excessive amount of H2 O2 in the presence of colorless substrates (S1 ) according to the rate law -d[S]/dt=kI kII [H2 O2 ][S][TAML]/(kI [H2 O2 ]+kII [S]+kII '[S1 ]). The bleaching rate is thus a descending hyperbolic function of S1   v=ab/(b+[S1 ]). Values of kII ’ found from a and b for phenol and propranolol with commonly used TAML [FeIII o,o’-C6 H4 (NCONMe2 CO)2 CMe2 2 (OH2 )]+ are consistent with those for S1 (phenol, propranolol) obtained directly by UPLC. The study sends vital messages to enzymologists and environmentalists. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.KRAS mutation is frequently seen in a subtype of ovarian cancer categorized as type 1. The KRAS-MAPK pathway, which is closely involved in type 1 cancer progression, is under the regulation of receptor tyrosine kinases (RTKs). AXL, one of the RTKs, has been reported to be overexpressed in ovarian cancer and contributes to the poor prognosis. However, there is no useful target-based agent against such gene profiles. We examined the combined effect of the dual RAF/MEK inhibitor CH5126766 and AXL inhibitor R428 on the growth of ovarian cancer HEY-T30 and OVCAR-5 cell lines, both of which bear KRAS mutation and express AXL at a high level, using the WST-8 assay and the colony formation assay. The synergistic effect of the combination was evaluated by the combination index. The apoptotic cells were analyzed by flow cytometry. The expression of apoptotic proteins and the phosphorylation of MAPK and AKT pathway proteins were investigated by Western blotting. We found that CH5126766 and R428 suppressed the phosphorylation of ERK and AKT, respectively, and their combination synergistically inhibited the growth of both cell lines with enhancement of apoptosis accompanied by the Bim up-regulation. Combined treatment with CH5126766 and R428 is expected as the novel therapeutic option for KRAS-mutated ovarian cancer with high expression of AXL. This article is protected by copyright. All rights reserved.ISSUES ADDRESSED The objective of this study was to explore the perceptions, barriers, and enablers to physical activity (PA) and minimising sedentary behaviour among Arab-Australians, a group who have lower levels of PA and higher rates of certain chronic diseases when compared with the general Australian population. METHODS A total of 28 Arab-Australians aged 35-64 years participated in one of five focus groups conducted in Western Sydney during 2017-2018, a culturally diverse region in New South Wales, Australia. Focus group duration ranged from 35-90 minutes with 4-7 participants in each group. Focus group data were recorded and transcribed verbatim and analysed using inductive thematic analysis. RESULTS Participants had a general understanding of PA and the associated health benefits. Fewer participants were aware of the independent health effects associated with prolonged sitting. A lack of time and motivation due to work, familial duties, domestic roles, and lack of effort reportedly influenced PA participation. Health was perceived to be both a barrier and an enabler to PA. Barriers related to health included pain and existing conditions and enablers included preventive and reactive measures. Social support and accessibility, such as a lack of support networks, the availability of services, and costs were also discussed. Cultural and religious influences, such as traditional gender roles and the importance of gender-exclusive settings, were also important factors influencing the PA behaviours of participants. CONCLUSIONS This study highlighted the factors that influence the PA levels and sedentary behaviour of Arab-Australian adults aged 35-64 years. SO WHAT? The findings of this study could help inform the design and development of culturally-tailored PA interventions for Arab-Australian adults. This article is protected by copyright. All rights reserved.Anal fistula is a common chronic perianal disease. The vast majority of anal fistulae are secondary to infection of the anal glands. Anal fistulae are classified according to their anatomic relation to the anal sphincter. The internal opening lies at the dentate line submucosal – runs under the anoderm or the rectal mucosa; intersphincteric – crosses the internal sphincter and reaches the skin; transsphincteric – crosses both sphincters; and suprasphincteric extend above the entire sphincter complex. This article is protected by copyright. All rights reserved.Growing tumors alter their metabolic profiles to support the increased cell proliferation. SETD1A, a histone lysine methyltransferase which specifically methylates H3K4, plays important roles in both normal cell and cancer cell functions. However, the function of SETD1A in gastric cancer (GC) progression and its role in GC metabolic reprogramming are still largely unknown. In the current study, we discovered that the expression of SETD1A was higher in GC tumor specimens compared to surrounding nontumor tissues. Upregulation of SETD1A increased GC cell proliferation, whereas downregulation of SETD1A inhibited GC cell proliferation. Furthermore, knockdown of SETD1A reduced glucose uptake and production of lactate and suppressed glycolysis by decreasing the expression of glycolytic genes, including GLUT1, HK2, PFK2, PKM2, LDHA, and MCT4. Mechanistically, SETD1A interacted with HIF1α to strengthen its transactivation, indicating that SETD1A promotes glycolysis through coactivation of HIF1α. SETD1A and HIF1α were recruited to the promoter of HK2 and PFK2, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on HK2 and PFK2 promoter and reduced HIF1α recruitment necessary to promote transcription of glycolytic genes. Inhibition of HIF1α decelerated SETD1A-enhanced GC cell growth. In additional, there was a linear correlation between SETD1A and several key glycolytic genes in human GC specimens obtained from TCGA dataset. Thus, our results demonstrated that SETD1A interacted with HIF1α to promote glycolysis and accelerate GC progression, implicating that SETD1A may be a potential molecular target for GC treatment. © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.OBJECTIVES During human pregnancy, the endothelial cells of the uterine spiral arteries (SPA) are extensively replaced by a subtype of placental trophoblasts, endovascular extravillous trophoblasts (enEVTs), thus establishing a placental-maternal circulation. On this pathway, foetus-derived placental villi and enEVTs bath into the maternal blood that perfuses along SPA being not attacked by the maternal lymphocytes. We aimed to reveal the underlying mechanism of such immune tolerance. METHODS In situ hybridization, immunofluorescence, ELISA and FCM assay were performed to examine TGF-β1 expression and distribution of regulatory T cells (Tregs) along the placental-maternal circulation route. The primary enEVTs, interstitial extravillous trophoblasts (iEVTs) and decidual endothelial cells (dECs) were purified by FACS, and their conditioned media were collected to treat naïve CD4+ T cells. Treg differentiation was measured by FLOW and CFSE assays. RESULTS We found that enEVTs but not iEVTs or dECs actively produced TGF-β1. The primary enEVTs significantly promoted naïve CD4+ T-cell differentiation into immunosuppressive FOXP3+ Tregs, and this effect was dependent on TGF-β1. In recurrent spontaneous abortion (RSA) patients, an evidently reduced proportion of TGF-β1-producing enEVTs and their ability to educate Tregs differentiation were observed. CONCLUSIONS Our findings demonstrate a unique immune-regulatory characteristic of placental enEVTs to develop immune tolerance along the placental-maternal circulation. New insights into the pathogenesis of RSA are also suggested. © 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.The use of biotechnological therapies for moderate-to-severe psoriasis is ever-expanding and it is becoming increasingly more frequent to encounter different unforeseen events during their use, such as fertile patients becoming pregnant and breast-feeding, development of infections due to personal habits like tuberculosis, HBV, HCV or HIV, scheduling of surgical procedures, need of vaccinations, development of malignancy and evaluation of dose tapering. As any clinician may experience at least one of these unexpected events, it should be good practice to know how to manage them. Thus, a practical analysis has been proposed in this paper. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.OBJECTIVE to investigate antenatal management and outcome in a large international cohort of spontaneous and post-laser twin anemia polycythemia sequence (TAPS). METHODS Data of monochorionic twins diagnosed antenatally with TAPS collected in the TAPS Registry between 2014-2019 were included in this study. Antenatal diagnosis of TAPS was based on middle cerebral artery peak systolic velocity (MCA-PSV) > 1.5 Multiples of the Median (MoM) in the TAPS donor and less then  1.0 MoM in the TAPS recipient. Cases were assigned to the management groups based on the first treatment that was received. The primary outcome included perinatal mortality and severe neonatal morbidity. The secondary outcome was diagnosis-to-birth interval. RESULTS In total, 370 TAPS cases were antenatally diagnosed and managed either with expectant management in 31% (113/370), laser surgery in 30% (110/370), intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)) in 19% (70/370), delivery in 12% (43/370), selectivrtality and morbidity were high in all management groups. Prolonging pregnancy was best achieved in expectant management, laser surgery and selective feticide. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.PURPOSE Low-field MRI offers favorable physical properties for SNR-efficient long readout acquisitions such as spiral and EPI. We used a 0.55 tesla (T) MRI system equipped with high-performance hardware to increase the sampling duty cycle and extend the TR of balanced steady-state free precession (bSSFP) cardiac cine acquisitions, which typically are limited by banding artifacts. METHODS We developed a high-efficiency spiral in-out bSSFP acquisition, with zeroth- and first-gradient moment nulling, and an EPI bSSFP acquisition for cardiac cine imaging using a contemporary MRI system modified to operate at 0.55T. Spiral in-out and EPI bSSFP cine protocols, with TR = 8 ms, were designed to maintain both spatiotemporal resolution and breath-hold length. Simulations, phantom imaging, and healthy volunteer imaging studies (n = 12) were performed to assess SNR and image quality using these high sampling duty-cycle bSSFP sequences. RESULTS Spiral in-out bSSFP performed favorably at 0.55T and generated good image quality, whereas EPI bSSFP suffered motion and flow artifacts. There was no difference in ejection fraction comparing spiral in-out with standard Cartesian imaging. Moreover, human images demonstrated a 79% ± 21% increase in myocardial SNR using spiral in-out bSSFP and 50% ± 14% increase in SNR using EPI bSSFP as compared with the reference Cartesian acquisition. Spiral in-out acquisitions at 0.55T recovered 69% ± 14% of the myocardial SNR at 1.5T. CONCLUSION Efficient bSSFP spiral in-out provided high-quality cardiac cine imaging and SNR recovery on a high-performance 0.55T MRI system. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.In addition to its regulatory role in luteinising hormone secretion, Rfamide-related peptide 3 (RFRP3) has also been reported to modulate food intake in several mammalian species. Djungarian hamsters (Phodopus sungorus), similar to other seasonal mammals, display a remarkable inhibition of RFRP3 expression in winter short-day conditions, associated with decreased food intake and bodyweight. This species is therefore a valuable model for assessing whether RFRP3 might be involved in the seasonal control of feeding behaviour and investigating its possible brain targets. We found that, although both male and female animals exhibit the same robust reduction in Rfrp expression in short- (SD) compared to long-day (LD) conditions, acute central administration of RFRP3 displays sex-dependent effects on food intake. RFRP3 increased food intake in female hamsters in SD or in LD dioestrus, but not in LD pro-oestrus, indicating that the orexigenic effect of RFRP3 is observed in conditions of low circulating oestradiol levels. In male hamsters, food intake was not changed by acute injections of RFRP3, regardless of whether animals were in SD or LD conditions. Analysing the gene expression of various metabolic neuropeptides in the brain of RFRP3-injected Djungarian hamsters revealed that Npy expression was increased in female but not in male animals. The present study suggests that, in Djungarian hamsters, RFRP3 exhibits a sex-dependent orexigenic effect possibly by inducing increased Npy expression. © 2020 British Society for Neuroendocrinology.A simple cobalt-diphosphine catalyst has been found to efficiently promote intramolecular cyclization of ortho -cyclopropylvinyl- and cyclopropylidenemethyl-substituted benzaldehydes into benzocyclooctadienone and benzocycloheptadienone derivatives, respectively. This ring-opening hydroacylation likely involves aldehyde C-H oxidative addition, olefin insertion, cyclopropane cleavage by β-carbon elimination, and C-C bond-forming reductive elimination, as supported by mechanistic experiments and DFT calculations. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Colistin is a last-line antibiotic against Gram-negative multidrug-resistant bacteria, but the increased resistance poses a huge challenge to this drug. However, the mechanisms underlying such resistance are largely unexplored. The present study first identified the mutations of two genes encoding AceF subunit of pyruvate dehydrogenase (PDH) and TetR family transcriptional regulator in colistin-resistant Vibrio alginolyticus (VA-RCT ) through genome sequencing. Then, gas chromatography-mass spectroscopy-based metabolomics was adopted to investigate metabolic responses since PDH plays a role in central carbon metabolism. Colistin resistance was associated with the reduction of the central carbon metabolism and energy metabolism, featuring the alteration of the pyruvate cycle, a recently characterized energy-producing cycle. Metabolites in the pyruvate cycle reprogramed colistin-resistant metabolome to colistin-sensitive metabolome, resulting in increased gene expression, enzyme activity or protein abundance of the cycle and sodium-translocating NADH-ubiquinone oxidoreductase. This reprogramming promoted the production of the proton motive force that enhances the binding between colistin and lipid A in lipopolysaccharide. Moreover, this metabolic approach was effective against VA-RCT in vitro and in vivo as well as other clinical isolates. These findings reveal a previously unknown mechanism of colistin resistance and develop a metabolome-reprogramming approach to promote colistin efficiency to combat with colistin-resistant bacteria. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The purpose of this study was to identify a correlation between the screening BI-RADS 0 (recall) rates and diagnostic BI-RADS 3 (short-interval follow-up) rates of individual interpreting radiologists, with the goal of utilizing the BI-RADS 3 rate as an acceptable performance metric in the diagnostic population. A multicenter retrospective analysis of medical audit statistics was conducted on annual radiologist performance data collected over a 14-year period in a community hospital-based practice. Mixed regression models were used to estimate the association between screening BI-RADS 0 and diagnostic BI-RADS 3 examinations while adjusting for calendar year, annual radiologist screening volume, annual radiologist diagnostic volume, and diagnostic examination indication. A moderate statistically significant positive correlation was established between the screening BI-RADS 0 rates and Diagnostic BI-RADS 3 rates (Pearson correlation coefficient + 0.349, P ≤ .001). Furthermore, when utilizing a national benchmark range of 8%-12% as an acceptable BI-RADS 0 rate within a screening population, the correlative BI-RADS 3 assessment rate was demonstrated to be approximately 16%. We propose that this BI-RADS category 3 rate may represent an additional acceptable performance metric in the diagnostic population. Routine inclusion of an interpreting mammographer’s diagnostic BI-RADS 3 rate in the annual medical audit may help reduce inappropriate and/or excess use of the BI-RADS 3 category, which may lead to significant potential reductions in follow-up examinations with their associated healthcare-related costs, resource expenditure, and induced patient anxiety. © 2020 Wiley Periodicals, Inc.A 30-year-old nulliparous woman was transferred under suspicion of acute appendicitis, due to the sudden onset of severe right lower quadrant pain at 31 weeks and 4 days of gestation. Magnetic resonance imaging showed a cystic mass measuring 40 mm in diameter in the right lower abdomen. Because the right ovary without edematous swelling was noted adjacent to the cystic mass, isolated tubal torsion was strongly suspected. Emergency gasless laparoendoscopic single-site surgery showed isolated torsion of the right fallopian tube with a paratubal cyst. The right ovary was not involved in this torsion. Because the color tone of the distal portion of the fallopian tube did not recover sufficiently after detorsion, right salpingectomy was performed. Postoperatively, the infusion of magnesium sulfate was initiated due to increased uterine contraction and continued until 36 weeks of gestation. At 38 weeks and 1 day of gestation, uneventful vaginal delivery yielded a healthy female infant. © 2020 Japan Society of Obstetrics and Gynecology.The use of mass antimicrobial treatment has been linked to the emergence of antimicrobial resistance in human and animal pathogens. Using whole genome (SMRT) sequencing, we characterized genomic variability of multidrug-resistant R. equi isolated from soil samples from 100 farms endemic for R. equi infections in Kentucky. We discovered the novel erm(51) encoding resistance to MLSB in R. equi isolates from soil of horse-breeding farms. erm(51) is inserted in a transposon (TnErm51), that is associated either with a putative conjugative plasmid (pRErm51), a mobilizable plasmid (pMobErm51), or both enabling horizontal gene transfer to susceptible organisms and conferring high levels of resistance against MLSB in vitro. This new resistant genotype also carries 2 previously unidentified rpoB mutations conferring resistance to rifampicin. Isolates carrying both vapA and erm(51) were rarely found, indicating either a recent acquisition of erm(51) and/or impaired survival when isolates carry both genes. Isolates carrying erm(51) are closely related genetically and were likely selected by antimicrobial exposure in the environment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.AIM The purpose of this study was to investigate the psychological and behavioural effects of animal-assisted therapy on cognitive function, emotional state, problematic behaviours, and activities of daily living among older adults with dementia. METHODS A nonequivalent control group pretest and post-test study design was used in this study. Twenty-eight participants-14 in the intervention group and 14 in the control group-were recruited from two hospitals in Gyeonggi Province, South Korea, between February and April 2015. The intervention group received two 60-min sessions of animal-assisted therapy weekly for 8 weeks, while the control group received conventional care. The cognitive function, emotional state (mood, depression), activities of daily living, and problematic behaviours of the two groups were compared at three points (before the study, at week 4, and at week 8). RESULTS The results showed significant group-by-time interactions of cognitive function (P  less then  0.001), mood status (P  less then  0.