The role of Probiotics in allergic diseases

Allergic disorders are very common in the pediatric age group. While the exact etiology is unclear, evidence is mounting to incriminate environmental factors and an aberrant gut microbiota with a shift of the Th1/Th2 balance towards a Th2 response. Probiotics have been shown to modulate the immune system back to a Th1 response. Several in vitro studies suggest a role for probiotics in treating allergic disorders. Human trials demonstrate a limited benefit for the use of probiotics in atopic dermatitis in a preventive as well as a therapeutic capacity. Data supporting their use in allergic rhinitis are less robust. Currently, there is no role for probiotic therapy in the treatment of bronchial asthma. Future studies will be critical in determining the exact role of probiotics in allergic disorders

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves.tThe 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

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

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570