The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

We review work on the paramagnetic amino acid 2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid, TOAC, and its applications in studies of peptides and peptide synthesis. TOAC was the first spin label probe incorporated in peptides by means of a peptide bond. In view of the rigid character of this cyclic molecule and its attachment to the peptide backbone via a peptide bond, TOAC incorporation has been very useful to analyze backbone dynamics and peptide secondary structure. Many of these studies were performed making use of EPR spectroscopy, but other physical techniques, such as X-ray crystallography, CD, fluorescence, NMR, and FT-IR, have been employed. The use of double-labeled synthetic peptides has allowed the investigation of their secondary structure. A large number of studies have focused on the interaction of peptides, both synthetic and biologically active, with membranes. In the latter case, work has been reported on ligands and fragments of GPCR, host defense peptides, phospholamban, and β-amyloid. EPR studies of macroscopically aligned samples have provided information on the orientation of peptides in membranes. More recent studies have focused on peptide–protein and peptide–nucleic acid interactions. Moreover, TOAC has been shown to be a valuable probe for paramagnetic relaxation enhancement NMR studies of the interaction of labeled peptides with proteins. The growth of the number of TOAC-related publications suggests that this unnatural amino acid will find increasing applications in the future

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI −16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI −29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View

Cryptococcal meningitis: A neglected NTD?

Although HIV/AIDS has been anything but neglected over the last decade, opportunistic infections (OIs) are increasingly overlooked as large scale donors shift their focus from acute care to prevention and earlier antiretroviral treatment (ART) initiation. Of these OIs, cryptococcal meningitis, a deadly invasive fungal infection, continues to affect hundreds of thousands of HIV patients with advanced disease each year and is responsible for an estimated 15%-20% of all AIDS-related deaths [1,2]. Yet cryptococcal meningitis ranks amongst the most poorly funded “neglected” diseases in the world, receiving 0.2% of available relevant research and development (RandD) funding according to Policy Cures’ 2016 G-Finder Report [3,4]

Unpublished Mediterranean and Black Sea records of marine alien, cryptogenic, and neonative species

To enrich spatio-temporal information on the distribution of alien, cryptogenic, and neonative species in the Mediterranean and the Black Sea, a collective effort by 173 marine scientists was made to provide unpublished records and make them open access to the scientific community. Through this effort, we collected and harmonized a dataset of 12,649 records. It includes 247 taxa, of which 217 are Animalia, 25 Plantae and 5 Chromista, from 23 countries surrounding the Mediterranean and the Black Sea. Chordata was the most abundant taxonomic group, followed by Arthropoda, Mollusca, and Annelida. In terms of species records, Siganus luridus, Siganus rivulatus, Saurida lessepsianus, Pterois miles, Upeneus moluccensis, Charybdis (Archias) longicollis, and Caulerpa cylindracea were the most numerous. The temporal distribution of the records ranges from 1973 to 2022, with 44% of the records in 2020–2021. Lethrinus borbonicus is reported for the first time in the Mediterranean Sea, while Pomatoschistus quagga, Caulerpa cylindracea, Grateloupia turuturu, and Misophria pallida are first records for the Black Sea; Kapraunia schneideri is recorded for the second time in the Mediterranean and for the first time in Israel; Prionospio depauperata and Pseudonereis anomala are reported for the first time from the Sea of Marmara. Many first country records are also included, namely: Amathia verticillata (Montenegro), Ampithoe valida (Italy), Antithamnion amphigeneum (Greece), Clavelina oblonga (Tunisia and Slovenia), Dendostrea cf. folium (Syria), Epinephelus fasciatus (Tunisia), Ganonema farinosum (Montenegro), Macrorhynchia philippina (Tunisia), Marenzelleria neglecta (Romania), Paratapes textilis (Tunisia), and Botrylloides diegensis (Tunisia).Stelios Katsanevakis, Michail Ragkousis, Maria Sini, Markos Digenis and Vasilis Gerovasileiou were supported by the Hellenic Foundation for Research and Innovation (HFRI) under the “First Call for HFRI Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant” (Project ALAS – “ALiens in the Aegean – a Sea under siege” (Katsanevakis et al. 2020b); Project Number: HFRI-FM17-1597). Konstantinos Tsirintanis was co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning”, 2014-2020, in the context of the Act “Enhancing Human Resources Research Potential by undertaking a Doctoral Research” Sub-action 2: IKY Scholarship Programme for PhD candidates in the Greek Universities. Maria Zotou was supported by the project “Coastal Environment Observatory and Risk Management in Island Regions AEGIS+” (MIS 5047038), implemented within the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020), co financed by the Hellenic Government (Ministry of Development and Investments) and the European Union (European Regional Development Fund, Cohesion Fund). Razy Hoffman was supported by Yad-Hanadiv Foundation, through the Israel Society of Ecology and Environmental Sciences and Israel Nature and Parks Authority, an integrated program for establishing biological baselines and monitoring protocols for marine reserves in the Israeli Mediterranean Sea (Grant #10669). Tatiana Begun, Adrian Teaca and Mihaela Muresan were supported by the European Union’s Horizon 2020 BRIDGE-BS project under grant agreement no. 101000240. Fiona Tomas was supported by the project “Invasion of the tropical alga Halimeda incrassata in the Balearic Islands: ecology and invasion dynamics (AAEE119/2017)”, funded by the Vicepresidencia y Consejería de Innovación, Investigación y Turismo del Govern de les Illes Balears, with support from the European Union and FEDER funds, and the project “Una nueva alga invasora en el Mediterráneo: invasibilidad, detección y erradicación del alga tropical Halimeda incrassata (INVHALI)”, funded by the Fundación Biodiversidad, del Ministerio para la Transición Ecológica y el Reto Demográfico. Simonetta Fraschetti, Laura Tamburello, Antonia Chiarore were supported by the project PO FEAMP 2014-2020 - DRD n. 35/2019, “Innovazione, sviluppo e sostenibilità nel settore della pesca e dell'acquacoltura per la Regione Campania” (ISSPA 2.51) and the EU EASME - EMFF (Sustainable Blue Econ-omy) Project AFRIMED (http://afrimed-project.eu/, grant agreement N. 789059). Carlos Jimenez, Louis Hadjioannou, Vasilis Resaikos, Valentina Fossati, Magdalene Papatheodoulou, and Antonis Petrou were supported by MedPan Small Projects, Mava, and LIFE-IP. Louis Hadjioannou, Manos L. Moraitis and Neophytos Agrotis received funding from the European Union’s Horizon 2020 research and innovation program within the framework of the CMMI/MaRITeC-X project under grant agreement No. 857586. Ernesto Azzurro was supported by the project USEIt - Utilizzo di Sinergie operative per la gestione integrata specie aliene Invasive in Italia, funded by the research programme @CNR. Antonietta Rosso and Francesco Sciuto were supported by the University of Catania through “PiaCeRi-Piano Incentivi per la Ricerca di Ateneo 2020–22 linea di intervento 2.” This is the Catania Paleoecological Research Group contribution n. 484. Diego K. Kersting was supported by the Beatriu de Pinós programme funded by the Secretary of Universities and Research (Government of Catalonia) and the Horizon 2020 programme of research and innovation of the European Union under the Marie Sklodowska-Curie grant agreement No 801370. Francesco Tiralongo was supported by the AlienFish project of Ente Fauna Marina Mediterranea (Scientific Organization for Research and Conservation of Marine Biodiversity, 96012 Avola, Italy), a citizen science project for monitoring and studying rare and non-indigenous fish in Italian waters. Adriana Vella, was supported by funds through the BioCon_Innovate Research Excellence Grant from the University of Malta awarded to her. Noel Vella was supported by REACH HIGH Scholars Programme-Post Doctoral Grant for the FINS project. Some of the records provided by Victor Surugiu were obtained during surveys carried out within the framework of the project “Adequate management of invasive species in Romania, in accordance with EU Regulation 1143/2014 on the prevention and management of the introduction and spread of invasive alien species”, SMIS 2014+ 120008, coordinated by the Romanian Ministry of Environment, Water and Forests in partnership with the University of Bucharest (2018–2022). Alan Deidun and Alessio Marrone were supported by the “Spot The Alien” citizen science campaign for the monitoring of the Alien species in the Maltese archipelago and by the Interreg Italia-Malta Harmony project. The authors from the National Institute of Biology (Slovenia) acknowledge the financial support of the Slovenian Research Agency (Research Core Funding No. P1-0237) and of the Ministry of Agriculture, Forestry and Food (project “Survey of the species richness and abundance of alien species in the Slovenian Sea”). Emanuele Mancini and Fabio Collepardo Coccia were supported by the project PO-FEAMP 2014-2020 “BIOBLITZ: research, knowledge and participation for the sustainable management of marine resources (BioBlitz Blu 2020)” coordinated by CURSA for MIPAAF, the Italian Ministry of Agricultural, Food and Forestry Policies, Measure 1.40 - Protection and restoration of biodiversity and marine ecosystems and compensation schemes in the context of sustainable fishing activities. Daniele Grech was supported by the PO-FEAMP 2014-2020 project ECOGESTOCK “Approccio ECOsistemico per la tutela e la GEStione delle risorse biologiche e STOCK ittici nelle acque interne”, the citizen science project Progetto Fucales: chi le ha viste? and the Paralenz Every dive counts sponsor. Jamila Rizgalla was supported by the project Snowball for the monitoring of alien species in Libyan waters له اهتفش له اهتدطصا ؟) have you seen it have you fished it?). Gerasimos Kondylatos and Dimitrios Mavrouleas were supported by the project “EXPLIAS” (MIS (ΟΠΣ): 5049912), design and piloting methods of commercial exploitation of invasive alien species with a view to contributing to their population control, coordinated by the National Technical University of Athens with the collaboration of the Hellenic Centre for Marine Research and the University of the Aegean and co-founded by Greece and the European Union. G. Kondylatos and Savvas Nikolidakis were supported by the project “SAMOS” (ID CODE: 32.2072004/001), a study for a submarine productive park in Marathokampos of Samos. Paraskevi K. Karachle, Aikaterini Dogrammatzi, Giorgos A. Apostolopoulos, Kassiani Konida and Melina Nalmpanti were supported by the project “4ALIEN: Biology and the potential economic exploitation of four alien species in the Hellenic Seas”, funded by NRSF 2017-2020 (MIS (ΟΠΣ): 5049511). Fabio Crocetta and Riccardo Virgili were partially funded by the project PO FEAMP Campania 2014–2020, DRD n. 35 of 15th March 2018, Innovazione, sviluppo e sostenibilità nel settore della pesca e dell’acquacoltura per la regione Campania, Misura 2.51, WP5, Task 5.5 Presenza e distribuzione di specie non indigene del macrozoobenthos e del necton in Campania. Michel Bariche was partially funded by the University Research Board of the American University of Beirut (DDF 103951/2592). Constantinos G. Georgiadis, Dimitra Lida Rammou, Paschalis Papadamakis and Sotiris Orfanidis were supported by the MSFD monitoring program. Sonia Smeraldo was supported by the MPA-Engage project, led by the Institute of Marine Sciences of the Spanish National Research Council and funded by the Interreg MED program. Evgeniia Karpova acknowledge that the publication of this article was in part carried out within the framework of the state assignment of the FRC IBSS “Patterns of Formation and Anthropogenic Transformation of Biodiversity and Bioresources of the Azov– Black Sea Basin and Other Regions of the World Ocean” (No. 121030100028-0). Elena Slynko’s work was carried out within the framework of a State Assignment no. 121051100109-1 of IBIW RAS. Manuela Falautano and Luca Castriota were supported by ISPRA citizen science campaigns for the monitoring of alien species through the dedicated institutional project ([email protected]). María Altamirano was supported by the project RUGULOPTERYX funded by Fundación Biodiversidad-Ministerio para la Transición Ecológica y el reto Demográfico (Spain) and the project UMA20-FEDERJA-006 with support from the European Union and FEDER funds and Junta de Andalucía. Records provided by L. Mangialajo were collected in the framework of projects funded by the Pew Charitable Trust, by the European Commission (AFRIMED, http://afrimed-project.eu/, grant agreement N. 789059) and by the Académie 3 de l’Université Côte d’Azur (projet CONVOST).Peer reviewe

Unpublished Mediterranean and Black Sea records of marine alien, cryptogenic, and neonative species

To enrich spatio-temporal information on the distribution of alien, cryptogenic, and neonative species in the Mediterranean and the Black Sea, a collective effort by 173 marine scientists was made to provide unpublished records and make them open access to the scientific community. Through this effort, we collected and harmonized a dataset of 12,649 records. It includes 247 taxa, of which 217 are Animalia, 25 Plantae and 5 Chromista, from 23 countries surrounding the Mediterranean and the Black Sea. Chordata was the most abundant taxonomic group, followed by Arthropoda, Mollusca, and Annelida. In terms of species records, Siganus luridus, Siganus rivulatus, Saurida lessepsianus, Pterois miles, Upeneus moluccensis, Charybdis (Archias) longicollis, and Caulerpa cylindracea were the most numerous. The temporal distribution of the records ranges from 1973 to 2022, with 44% of the records in 2020–2021. Lethrinus borbonicus is reported for the first time in the Mediterranean Sea, while Pomatoschistus quagga, Caulerpa cylindracea, Grateloupia turuturu, and Misophria pallida are first records for the Black Sea; Kapraunia schneideri is recorded for the second time in the Mediterranean and for the first time in Israel; Prionospio depauperata and Pseudonereis anomala are reported for the first time from the Sea of Marmara. Many first country records are also included, namely: Amathia verticillata (Montenegro), Ampithoe valida (Italy), Antithamnion amphigeneum (Greece), Clavelina oblonga (Tunisia and Slovenia), Dendostrea cf. folium (Syria), Epinephelus fasciatus (Tunisia), Ganonema farinosum (Montenegro), Macrorhynchia philippina (Tunisia), Marenzelleria neglecta (Romania), Paratapes textilis (Tunisia), and Botrylloides diegensis (Tunisia).peer-reviewe

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat