A human iPSC line capable of differentiating into functional macrophages expressing ZsGreen: a tool for the study and in vivo tracking of therapeutic cells

We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity. The high level of ZsGreen expression had no effect on the ability of macrophages to be activated to an M(LPS + IFNγ), M(IL10) or M(IL4) phenotype nor on their plasticity, assessed by their ability to switch from one phenotype to another. Thus, targeting of the AAVS1 locus in iPSCs allows for the production of fully functional, fluorescently tagged human macrophages that can be used for in vivo tracking in disease models. The strategy also provides a platform for the introduction of factors that are predicted to modulate and/or stabilize macrophage function. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’

Soluble/MOF-Supported Palladium Single Atoms Catalyze the Ligand-, Additive-, and Solvent-Free Aerobic Oxidation of Benzyl Alcohols to Benzoic Acids

Metal single-atom catalysts (SACs) promise great rewards in terms of metal atom efficiency. However, the requirement of particular conditions and supports for their synthesis, together with the need of solvents and additives for catalytic implementation, often precludes their use under industrially viable conditions. Here, we show that palladium single atoms are spontaneously formed after dissolving tiny amounts of palladium salts in neat benzyl alcohols, to catalyze their direct aerobic oxidation to benzoic acids without ligands, additives, or solvents. With this result in hand, the gram-scale preparation and stabilization of Pd SACs within the functional channels of a novel methyl-cysteine-based metal-organic framework (MOF) was accomplished, to give a robust and crystalline solid catalyst fully characterized with the help of single-crystal X-ray diffraction (SCXRD). These results illustrate the advantages of metal speciation in ligand-free homogeneous organic reactions and the translation into solid catalysts for potential industrial implementation.This work was supported by the Ministero dell’Istruzione, dell’Università e della Ricerca (Italy) and the MINECO (Spain) (Projects PID2019−104778GB−I00, CTQ 2017–86735–P, RTC–2017–6331–5, Severo Ochoa program SEV–2016–0683 and Excellence Unit “Maria de Maeztu” CEX2019−000919−M). E.T. and M.M. thank MINECO and ITQ for the concession of a contract. D.A. acknowledges the financial support of the Fondazione CARIPLO/“Economia Circolare: ricerca per un futuro sostenibile” 2019, Project code: 2019–2090, MOCA and Diamond Light Source for awarded beamtime and provision of synchrotron radiation facilities and thanks Dr. Sarah Barnett and David Allan for their assistance at I19 beamline (Proposal No. MT18768-1). Thanks are also extended to the “2019 Post-doctoral Junior Leader-Retaining Fellowship, la Caixa Foundation (ID100010434 and fellowship code LCF/BQ/PR19/11700011” (J.F.-S.) and “La Caixa” scholarship (ID 100010434) LCF/BQ/DI19/11730029 (J.B.-S). E.P. acknowledges the financial support of the European Research Council under the European Union’s Horizon 2020 research and innovation programme/ERC Grant Agreement No 814804, MOF reactors. J.O.-M. acknowledges the Juan de la Cierva program for the concession of a contract (IJC2018-036514-I). We gratefully acknowledge to ALBA synchrotron for allocating beamtime and CLÆSS beamline staff for their technical support during our experiment. The computations were performed on the Tirant III cluster of the Servei d’Informàtica of the University of Valencia.Peer reviewe

Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension

Background: Imbalance between cell proliferation and apoptosis underlies the development of pulmonary arterial hypertension (PAH). Current vasodilator treatment of PAH does not target the uncontrolled proliferative process in pulmonary arteries. Proteins involved in the apoptosis pathway may play a role in PAH and their inhibition might represent a potential therapeutic target. Survivin is a member of the apoptosis inhibitor protein family involved in cell proliferation.Objectives: This study aimed to explore the potential role of survivin in the pathogenesis of PAH and the effects of its inhibition.Methods: In SU5416/hypoxia-induced PAH mice we assessed the expression of survivin by immunohistochemistry, western-blot analysis, and RT-PCR; the expression of proliferation-related genes (Bcl2 and Mki67); and the effects of the survivin inhibitor YM155. In explanted lungs from patients with PAH we assessed the expression of survivin, BCL2 and MKI67.Results: SU5416/hypoxia mice showed increased expression of survivin in pulmonary arteries and lung tissue extract, and upregulation of survivin, Bcl2 and Mki67 genes. Treatment with YM155 reduced right ventricle (RV) systolic pressure, RV thickness, pulmonary vascular remodeling, and the expression of survivin, Bcl2, and Mki67 to values similar to those in control animals. Lungs of patients with PAH also showed increased expression of survivin in pulmonary arteries and lung extract, and also that of BCL2 and MKI67 genes, compared with control lungs.Conclusion: We conclude that survivin might be involved in the pathogenesis of PAH and that its inhibition with YM155 might represent a novel therapeutic approach that warrants further evaluation

Monografies del Montseny - 37

Antoni Pladevall Font va fer possible el naixement de la col.lecció completa de les Monografies del Montseny, n’ha estat el director durant molts anys, ha publicat més de seixanta treballs d’investigació històrica, i ha estat el mestre que ha mostrat el camí a seguir en la tasca d’aprofundiment de la història del Montseny i el seu entorn més proper. En el pròleg del volum 37 de les Monografies del Montseny es glosa la figura d’Antoni Pladevall Font, qui l’any 1966 inicià la col·laboració en el Servei de Conservació i Catalogació de Monuments Històrics a la Diputació de Barcelona; dos anys més tard, passà a exercir com a professor d’història medieval a la Facultat de Teologia de Barcelona. Obtingué el títol d’Arxiver Municipal de Vic l’any 1979, mentre treballa a la Diputació, i al 1981començà a treballar en el Departament de Cultura de la Generalitat fins a la seva jubilació l’any 1999. L’aleshores conseller de Cultura de la Generalitat Max Cahner li va encarregar d’organitzar el Servei de Conservació i Restauració de Monuments Arquitectònics on se li va assignar la secció d’inventari i la de cap de servei en funcions. Dos anys després hi va exercir com a director general del Patrimoni Arquitectònic. En aquesta etapa va col·laborar amb la Fundació i Editorial de la Gran Enciclopèdia Catalana, en la qual va exercir la direcció d’obres tan importants com la “Catalunya Romànica” i “L’Art Gòtic de Catalunya”, i va assessorar la “Gran Geografia Comarcal de Catalunya”.Objectius de Desenvolupament Sostenible::11 - Ciutats i Comunitats SosteniblesObjectius de Desenvolupament Sostenible::4 - Educació de QualitatPostprint (published version

Effectiveness of manual therapies: the UK evidence report

<p>Abstract</p> <p>Background</p> <p>The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions.</p> <p>Methods</p> <p>The conclusions are based on the results of systematic reviews of randomized clinical trials (RCTs), widely accepted and primarily UK and United States evidence-based clinical guidelines, plus the results of all RCTs not yet included in the first three categories. The strength/quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs.</p> <p>Results</p> <p>By September 2009, 26 categories of conditions were located containing RCT evidence for the use of manual therapy: 13 musculoskeletal conditions, four types of chronic headache and nine non-musculoskeletal conditions. We identified 49 recent relevant systematic reviews and 16 evidence-based clinical guidelines plus an additional 46 RCTs not yet included in systematic reviews and guidelines.</p> <p>Additionally, brief references are made to other effective non-pharmacological, non-invasive physical treatments.</p> <p>Conclusions</p> <p>Spinal manipulation/mobilization is effective in adults for: acute, subacute, and chronic low back pain; migraine and cervicogenic headache; cervicogenic dizziness; manipulation/mobilization is effective for several extremity joint conditions; and thoracic manipulation/mobilization is effective for acute/subacute neck pain. The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration, and for manipulation/mobilization for mid back pain, sciatica, tension-type headache, coccydynia, temporomandibular joint disorders, fibromyalgia, premenstrual syndrome, and pneumonia in older adults. Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham manipulation, or for Stage 1 hypertension when added to an antihypertensive diet. In children, the evidence is inconclusive regarding the effectiveness for otitis media and enuresis, and it is not effective for infantile colic and asthma when compared to sham manipulation.</p> <p>Massage is effective in adults for chronic low back pain and chronic neck pain. The evidence is inconclusive for knee osteoarthritis, fibromyalgia, myofascial pain syndrome, migraine headache, and premenstrual syndrome. In children, the evidence is inconclusive for asthma and infantile colic.</p

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research