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Accurate identification of precipitating clouds is a challenging task. In the present work, Support Vector Machines, Decision Trees and Random Forests algorithms were applied to discriminate between precipitating clouds and non-precipitating clouds from a satellite weather image GOES-13 covering the Colombian territory. The objective of this study was to evaluate the performance of machine learning (ML) algorithms for digital classification of cloud masses in terms of thematic accuracy classification using the conventional Mahalanobis algorithm as benchmark. Results show that ML algorithms provide more accurate classification of cloud masses than conventional algorithms. The best accuracy was obtained using Random Forests (RF), with an overall thematic accuracy of 97%. Furthermore, the classification obtained with the RF algorithm was compared pixel-to-pixel with NASA Tropical Rainfall Measurement Mission (TRMM) rainfall estimates, obtaining an overall accuracy of 94%. ML algorithms can therefore be used to improve current precipitating clouds identification methods.

Extensive nonmaternal childcare plays an important role in children's development. This study examined a potential coping mechanism for dealing with daily separation from caregivers involved in childcare experience—children's development of attachments toward inanimate objects. We employed the twin design to estimate relative environmental and genetic contributions to the presence of object attachment, and assess whether childcare explains some of the environmental variation in this developmental phenomenon. Mothers reported about 1122 3-year-old twin pairs. Variation in object attachment was accounted for by heritability (48%) and shared environment (48%), with childcare quantity accounting for 2.2% of the shared environment effect. Children who spent half-days in childcare were significantly less likely to attach to objects relative to children who attended full-day childcare.

Purpose. To study the contribution of a novel PAF receptor antagonist LAU-0901 in the modulation of the increased inflammatory response in mice exposed to dessicating conditions (DE) after PRK. Methods. Eighty 13-14 week old female Balb/C mice were used. They were divided into two groups: One group was treated with LAU-0901 topical drops. The other group was treated with vehicle. In each group ten mice served as controls and ten were placed in DE. The other twenty mice underwent bilateral PRK and were divided in two additional groups: ten mice remained under normal conditions (NC) and the other ten were exposed to DE. After 1 week all animals underwent in vivo confocal microscopy, immunostaining and western blotting analysis. Results. Confocal microscopy showed an increased number of reflective structures in the corneal epithelium after PRK and exposure to DE in eyes treated with vehicle as compared to eyes treated with LAU-0901. Significant decrease of COX-2 and Arginase I expression and reduced alpha SMA cells was observed after PRK and exposure to DE in eyes treated with LAU-0901. Discussion: Exposure of mice to a DE after PRK increases the epithelial turnover rate. PAF is involved in the inflammatory cell infiltration and expression of inflammatory cytokines that follow PRK under DE.

During the past 60 years, intensive genetic selection has increased the growth rate of broiler (meat-type) chickens by more than 300%. However, these improvements in growth rate and feed efficiency are accompanied by higher incidence of skeletal abnormalities, especially leg deformities with poor walking ability and locomotion. Whether these disorders are direct effects of the growth rate or indirect effects that result from increased body weight and improper development of bone, muscles and/or tendons is still unknown. Tibial dyschondroplasia (TD) is a bone disorder frequently observed in broilers and turkeys flocks. It is a disease of the growth plate (GP) at the ends of long bones, which is characterized by enlargement of the GP, abnormal chondrocyte differentiation, and a major decrease in blood vessels and perfusion. Based on our preliminary results, we hypothesize that increase in angiogenesis, and improved oxygen supply to the growth plate, will lead to amelioration of lameness in TD. Improving angiogenesis can be achieved by reducing oxygen level and exposing the developing embryo to hypoxic condition. The aim of this study was to investigate the effect of hypoxic microenvironment during embryonic limb bud development (E6 to E9) on bone disorders. Fertile Cobb strain broiler chicken eggs (n = 400) were incubated under standard incubation conditions. At E6 the eggs were randomly allocated to four treatments: control; 17% O2, 13% O2 and 11% O2 concentration for 12 h/d from E6 through E9. Our results show that 11% O2 is the biological limit for hypoxic adaptation, resulting in embryonic mortality at the first day of exposure. GP histology and vascular quantification at time of hatch and D7 of the three remaining treatments reviled, that the 13% treatment significantly affected vascular area density of the GP and in this group the GP blood system was dense with a higher blood vessel complexity. A higher vascular density area of the GP coincided with a positive effect on TD occurrences. Following thiram administration (which serves as an agent to challenge GP formation) to the feed (40 ppm), and TD scoring, incidence of TD in the control group was found to be 78%. TD incidence in the 17% group was 57% while in the 13% TD incidence was only 57%, significantly lower compare to control. Thus, our results suggest that hypoxic exposure to 13% oxygen concentration during the limb bud development increase angiogenesis, and improved oxygen supply to the GP, hence it reduces chicks' susceptibility to TD. [ABSTRACT FROM AUTHOR]

The application of methane as a fuel in the automotive industry shows an increasing tendency, but its release into the atmosphere is detrimental due to its very high greenhouse effect. For this reason, new solutions for cleaning systems of exhaust gas from methane engines are in demand. This study focuses on thorough characterisation of active centres, structure-activity relationships, and reaction steps on palladium ceria supported catalysts of different loading, using the in situ FTIR method with different surface probe molecules. The results show substantial activity of low loading Pd/CeO2 catalyst, correlated with its high dispersion. Three types of active centres were found on the catalyst surface: acidic and redox on both the ceria and palladium oxide surfaces, and basic ones on the palladium oxide. The reaction on the Pd/CeO2 catalyst was shown to proceed via the formation of monodentates, which were a stable reaction intermediate in the temperature range between 150 and 250 °C. The assignment of the intermediates was supported by the in situ FTIR sorption experiments with CO, CH4 used as probe molecules. [ABSTRACT FROM AUTHOR]

• Native osteomyelitis caused by ESBL-producing Enterobacteriaceae remains a rare condition. • Osteomyelites caused by Klebsiella pneumoniae appeared to be associated with an unfavourable outcome. • Treatment is complex and mainly based on combination therapy with carbapenems. Antibiotic treatment of native osteomyelitis caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) is a challenge. Limited epidemiological and outcome data are available. This retrospective cohort study included osteomyelitis patients with ESBL-PE infections treated in a reference centre for bone and joint infections (BJIs) between 2011–2019. Twenty-nine patients with native BJI (mean age, 44.4 ± 15.7 years) were analysed. Fifteen cases were paraplegic patients with ischial pressure sores breaching the hip capsule. Other cases included eight other hip infections, four tibial infections and two foot infections. Infections were mostly polymicrobial (n = 23; 79.3%), including Staphylococcus aureus (n = 13; 8 methicillin-resistant). Klebsiella pneumoniae (n = 13) was the most frequent ESBL-producing species identified, followed by Escherichia coli (n = 10), including 3 E. coli / K. pneumoniae co-infections, and Enterobacter spp. (n = 9). ESBL-PE were rarely susceptible to fluoroquinolones (n = 4; 13.8%). Most therapies were based on carbapenems (n = 22) and combination therapies (n = 19). The median duration of treatment was 41 (5–60) days. Primary control of the infection was achieved in 62.1% (18/29) of cases and up to 86.2% after second look surgeries, after a median follow-up of 6 (1–36) months. Infection with ESBL-producing K. pneumoniae was associated with failure (P = 0.001), whereas age, infection location, prior colonisation and antimicrobial therapy were not found to be predictors of outcome. ESBL-PE native BJIs are often polymicrobial and fluoroquinolone-resistant infections caused by K. pneumoniae , highlighting the need for expert centres with pluridisciplinary meetings with experienced surgeons. [ABSTRACT FROM AUTHOR]

La chirurgie pancréatique majeure est associée à une importante morbidité, principalement infectieuse, conduisant certains auteurs à proposer une antibiothérapie postopératoire systématique. Cette attitude n'est néanmoins pas consensuelle et les pratiques antibiotiques varient significativement d'un centre à l'autre. Ces prescriptions exposent en outre les patients aux complications potentielles de l'antibiothérapie et aux risques d'émergence de résistance bactérienne. L'objectif de ce travail était d'étudier les pratiques de l'antibiothérapie postopératoire de chirurgie pancréatique majeure et d'identifier des facteurs associés à la survenue d'une infection qui pourraient aider à en préciser les indications. Nous avons mené une étude rétrospective monocentrique dans un centre hospitalo-universitaire. De janvier 2007 à novembre 2018, les patients ayant subi une chirurgie pancréatique majeure réglée ont été inclus dans l'étude. Le critère principal de jugement concernait la prescription systématique postopératoire d'antibiotique (ATB) et la survenue d'une infection du site opératoire (ISO). L'objectif secondaire était d'étudier les facteurs associés aux infections postopératoires (ISO, pneumonie, bactériémie) afin d'identifier les critères cliniques et/ou biologiques pouvant influencer la prescription d'antibiotiques. Cent quarante-neuf patients (115 duodéno-pancréatectomies céphaliques, 34 spléno-pancréatectomies caudales) ont été inclus. Trente patients (20,1 %) ont présenté une ISO et 72 (28,2 %) ont reçu une antibiothérapie systématique. La prescription d'une antibiothérapie postopératoire était similaire entre les groupes de patients ISO+ et ISO− (26,7 versus 28,6 %, p = 0,9). Quatre-vingt-quatre patients (57 %) appartenant au groupe ATB− n'ont pas développé d'ISO, alors que 22 (14,8 %) du même groupe ont développé une ISO. Ces derniers présentaient une mortalité hospitalière significativement plus élevée que les patients du groupe ATB−/ISO− (18,2 versus 0 %, p = 0,002), mais identique aux patients du groupe ATB+/ISO+. La présence d'une prothèse biliaire était similaire dans les groupes ATB−/ISO− et ATB−/ISO+. Une fièvre était plus fréquemment notée dans le groupe ATB−/ISO+ (72,7 versus 33,3 %, p = 0,001). En analyse multivariée, la fièvre était indépendamment associée à la survenue d'une ISO (odds ratio 6,24 [2,4–18,57], p < 0,001). Dans cette série monocentrique, l'antibiothérapie postopératoire systématique après chirurgie pancréatique majeure a été évitée sans conséquence sur la survenue d'une ISO chez plus de la moitié des patients. Cette attitude d'épargne est à mettre en balance avec la survenue d'une ISO responsable d'une surmortalité, mais la fièvre postopératoire semble être un paramètre clinique pertinent pour traiter sans délai une telle complication. [ABSTRACT FROM AUTHOR]

Introduction Les septicémies sont fréquentes dans la population gériatrique, mais leur épidémiologie et leur pronostic sont mal connus. Nous nous sommes intéressés aux caractéristiques cliniques et microbiologiques des septicémies dans cette population et à la prévalence des bactéries multirésistantes (BMR). Matériels et méthodes Étude rétrospective sur 6 ans (1 er avril 2011–31 décembre 2016) dans un hôpital universitaire gériatrique de 658 lits. Tous les patients hospitalisés ayant des hémocultures positives ont été identifiés. Après exclusion des contaminants, les dossiers médicaux ont été revus de manière pluridisciplinaire (infectiologues, gériatres, pharmaciens). Une septicémie était définie par l’association d’au moins une hémoculture positive et la prescription d’un traitement antibiotique systémique correspondant. La sévérité initiale de l’épisode était définie par l’existence d’au moins un des critères suivants : expansion volémique, ventilation mécanique, administration d’amines vasopressives ou admission en unité de soins intensifs. Le critère de jugement principal était la guérison à j28 après la septicémie ou à la sortie de l’hôpital. Le décès était considéré comme lié à l’infection en cas de persistance ou de réapparition de signes septiques au moment du décès lors du suivi. Résultats Au total, 261 septicémies ont été colligées, puis 68 contaminants ont été exclus. L’âge moyen était de 87,1 ans, le sexe-ratio (H/F) était de 1,1. Les principaux antécédents étaient : néoplasie (22,3 %), diabète (16,6 %) et immunodépression (10,4 %). Les sources d’infection étaient urinaire (53,4 %), respiratoire (10,4 %), intra-abdominale (6,2 %), cutanée (5,7 %) et primitive (15,1 %). Les principales bactéries impliquées étaient : E. coli (47,7 %), S. aureus (14,0 %), Enterococcus spp. (10,4 %), staphylocoques à coagulase négative (8,3 %), Klebsiella spp. (7,3 %) et P. aeruginosa (6,2 %). L’épisode était sévère dans 24,9 % des cas, le taux de guérison était de 64,6 % et la mortalité globale de 21,7 %. Le décès était considéré comme lié à l’infection dans 78,9 % des cas. Concernant les infections à BMR, leur proportion semble stable dans le temps : 10,7 % (2011–2012), 19,6 % (2013–2014) et 14,8 % (2015–2016). Il n’existait pas de différence significative entre les infections dues aux BMR et aux non-BMR concernant les comorbidités, les caractéristiques cliniques, la porte d’entrée, les bactéries impliquées et la sévérité sauf le taux de guérison qui était de 46,2 % vs. 70,6 % ( p = 0,004) pour les infections à BMR vs. non-BMR. Conclusion Les septicémies dans la population gériatrique sont fréquentes et leur mortalité est importante. La prévalence des BMR est stable dans le temps, mais ces dernières sont associées à pronostic plus péjoratif. [ABSTRACT FROM AUTHOR]

Introduction Les endocardites infectieuses (EI) sont des pathologies graves, dont la prise en charge pluridisciplinaire est recommandée. Nous nous sommes intéressés aux différences selon le pathogène incriminé dans notre cohorte d’EI suivie de manière pluridisciplinaire. Matériels et méthodes Cohorte prospective comparative d’EI suivie 1 an post-fin de traitement par une équipe pluridisciplinaire de 2016 à 2017. Toutes les suspicions d’EI de notre hôpital sont revues par une équipe pluridisciplinaire (infectiologue, cardiologue, réanimateur, microbiologiste, chirurgien et radiologue) qui statue sur le diagnostic définitif, le bilan à réaliser et la stratégie thérapeutique. Présentation des caractéristiques cliniques, microbiologiques et pronostiques selon la bactérie identifiée. Une différence était considérée comme significative si p < 0,05. Résultats Au total, 32 suspicions d’EI ont été vus par l’équipe pluridisciplinaire, 26 ont été retenues avec le diagnostic d’EI et inclues dans la cohorte dans un hôpital universitaire de 545 lits de MCO. Un seul patient a présenté une EI à Pseudomonas aeruginosa . Parmi les 25 cas restants, on dénombrait 7 EI à streptocoque, 9 à entérocoque et 9 à Staphylococcus aureus . L’âge moyen global était de 71,0 ans. Parmi les antécédents, 9 (36,0 %) patients étaient diabétiques et 12 (48,0 %) présentaient une valvulopathie sans différence significative selon le type de bactérie incriminée. Un matériel intracardiaque était présent dans 13 cas (52,0 %) et était significativement plus fréquent en cas d’endocardite à entérocoque (66,7 %) et à S. aureus (66,7 %). Les patients présentaient de la fièvre dans 21 cas (84,0 %) et significativement moins fréquemment au cours des EI à entérocoque (55,6 %). Globalement, les patients bénéficiaient d’une intervention dans 7 (28,0 %) cas. Le taux de décès était de 32,0 %. Les EI à S. aureus étaient significativement associées à plus de complications cardiaques liées à une destruction valvulaire (77,8 % vs 56,0 %), plus de choc septique (44,4 % vs 16,0 %), et plus de prise en charge en réanimation (88,9 % vs 60,0 %) et de décès (44,4 % vs 32,0 %). Mais, elles n’étaient pas significativement associées à plus de complications neurologiques (33,3 % vs 36,0 %). Conclusion Au cours des EI, les EI à entérocoque semblent plus souvent apyrétique et plus souvent liées à des dispositifs intracardiaques, alors que les EI à Staphylococcus aureus semblent associées à une mortalité plus importante liée à des complications cardiaques et septiques, mais pas à des complications neurologiques. [ABSTRACT FROM AUTHOR]

A combined direct and inverse photoemission study of coinage metal corroles suggests that the latter technique, in favorable cases, can provide some additional information relative to electrochemical measurements. Thus, whereas inverse photoemission spectroscopy (IPES) provides relative electron affinities for electron addition to different unoccupied orbitals, electrochemical reduction potentials shed light on the energetics of successive electron additions. While all three coinage metal triphenylcorrole (TPC) complexes exhibit similar ionization potentials, they exhibit dramatically different inverse photoemission spectra. For Cu[TPC], the lowest-energy IPES feature (0.74 eV) is found to be exceedingly close to the Fermi level; it is significantly higher for Ag[TPC] (1.65 eV) and much higher for Au[TPC] (2.40 eV). These differences qualitatively mirror those observed for electrochemical reduction potentials and are related to a partially metal-centered LUMO in the case of Cu- and Ag[TPC] and a fully corrole-based LUMO in the case of Au[TPC]; the latter orbital corresponds to the LUMO+1 in the case of Ag[TPC]., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Cytotoxic T lymphocyte (CTL) motility is an important feature of effective CTL responses and is impaired when CTLs become exhausted, e.g. during chronic retroviral infections. A prominent T cell exhaustion marker is programmed cell death protein 1 (PD-1) and antibodies against the interaction of PD-1 and PD-ligand 1 (PD-L1) are known to improve CTL functions. However, antibody blockade affects all PD-1/PD-L1-expressing cell types, thus, the observed effects cannot be attributed selectively to CTLs. To overcome this problem, we performed CRISPR/Cas9 based knockout of the PD-1 coding gene PDCD1 in naïve Friend Retrovirus (FV)-specific CTLs. We transferred 1,000 of these cells into mice where they proliferated upon FV-infection. Using intravital two-photon microscopy we visualized CTL motility in the bone marrow and evaluated cytotoxic molecule expression by flow cytometry. Knockout of PDCD1 improved the CTL motility at 14 days post infection and enhanced the expression of cytotoxicity markers. Our data show the potential of genetic tuning of naive antiviral CTLs and might be relevant for future designs of improved T cell-mediated therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mittermüller, Otto, Kilian, Schnormeier, Littwitz-Salomon, Hasenberg, Dittmer and Gunzer.)

Tumor cells rely heavily on glycolysis to meet their high metabolic demands. While this results in nutrient deprivation within the tumor microenvironment and has negative effects on infiltrating immune cells such as natural killer (NK) cells, it also creates a potential target for cancer therapies. Here we use Glupin, an inhibitor of glucose transporters, to study the effect of limited glucose uptake on NK cells and their anti-tumor functions. Glupin treatment effectively inhibited glucose uptake and restricted glycolysis in NK cells. However, acute treatment had no negative effect on NK cell cytotoxicity or cytokine production. Long-term restriction of glucose uptake via Glupin treatment only delayed NK cell proliferation, as they could switch to glutaminolysis as an alternative energy source. While IFN-γ production was partially impaired, long-term Glupin treatment had no negative effect on degranulation. Interestingly, the serial killing activity of NK cells was even slightly enhanced, possibly due to changes in NAD metabolism. This demonstrates that NK cell cytotoxicity is remarkably robust and insensitive to metabolic disturbances, which makes cellular metabolism an attractive target for immune-mediated tumor therapies.

Objectives: Quality assurance of breast imaging has a long history of using test objects to optimize and follow up imaging devices. In particular, the evaluation of new techniques benefits from suitable test objects. The applicability of a phantom consisting of spiculated masses to assess image quality and its dependence on dose in flat field digital mammography (FFDM) and digital breast tomosynthesis systems (DBT) is investigated., Methods: Two spiculated masses in five different sizes each were created from a database of clinical tumour models. The masses were produced using 3D printing and embedded into a cuboid phantom. Image quality is determined by the number of spicules identified by human observers., Results: The results suggest that the effect of dose on spicule detection is limited especially in cases with smaller objects and probably hidden by the inter-reader variability. Here, an average relative inter-reader variation of the counted number of 31% was found (maximum 83%). The mean relative intra-reader variability was found to be 17%. In DBT, sufficiently good results were obtained only for the largest masses., Conclusions: It is possible to integrate spiculated masses into a cuboid phantom. It is easy to print and should allow a direct and prompt evaluation of the quality status of the device by counting visible spicules. Human readout presented the major uncertainty in this study, indicating that automated readout may improve the reproducibility and consistency of the results considerably., Advances in Knowledge: A cuboid phantom including clinical objects as spiculated lesion models for visual assessing the image quality in FFDM and DBT was developed and is introduced in this work. The evaluation of image quality works best with the two larger masses with 21 spicules., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Natural killer (NK) cells are cytotoxic innate immune cells, able to recognize and eliminate virus-infected as well as cancer cells. Metabolic reprogramming is crucial for their activity as they have enhanced energy and nutritional demands for their functions during an infection. Fatty acids (FAs) represent an important source of cellular energy and are essential for proliferation of immune cells. However, the precise role of FAs for NK cells activity in retrovirus infection was unknown. Here we show that activated NK cells increase the expression of the FA uptake receptor CD36 and subsequently the uptake of FAs upon acute virus infection. We found an enhanced flexibility of NK cells to utilize FAs as source of energy compare to naïve NK cells. NK cells that were able to generate energy from FAs showed an augmented target cell killing and increased expression of cytotoxic parameters. However, NK cells that were unable to generate energy from FAs exhibited a severely decreased migratory capacity. Our results demonstrate that NK cells require FAs in order to fight acute virus infection. Susceptibility to severe virus infections as it is shown for people with malnutrition may be augmented by defects in the FA processing machinery, which might be a target to therapeutically boost NK cell functions in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schimmer, Mittermüller, Werner, Görs, Meckelmann, Finlay, Dittmer and Littwitz-Salomon.)

The interplay between hypoxia-inducible factors (HIFs) and transforming growth factor beta (TGF-β) is critical for both inflammation and angiogenesis. In hereditary hemorrhagic telangiectasia (HHT), we have previously observed that impairment of the TGF-β pathway is associated with downregulation of HIF-1α. HIF-1α accumulation is mandatory in situations of altered energy demand, such as during infection or hypoxia, by adjusting cell metabolism. Leukocytes undergo a HIF-1α-dependent switch from aerobic mitochondrial respiration to anaerobic glycolysis (glycolytic switch) after stimulation and during differentiation. We postulate that the decreased HIF-1α accumulation in HHT leads to a clinically observed immunodeficiency in these patients. Examination of HIF-1α and its target genes in freshly isolated peripheral blood mononuclear cells (PBMCs) from HHT patients revealed decreased gene expression and protein levels of HIF-1α and HIF-1α-regulated glycolytic enzymes. Treatment of these cells with the HIF-prolyl hydroxylase inhibitor, Roxadustat, rescued their ability to accumulate HIF-1α protein. Functional analysis of metabolic flux using a Seahorse FX extracellular flux analyzer showed that the extracellular acidification rate (indicator of glycolytic turnover) after Roxadustat treatment was comparable to non-HHT controls, while oxygen consumption (indicator of mitochondrial respiration) was slightly reduced. HIF stabilization may be a potential therapeutic target in HHT patients suffering from infections.

Background: We report the 4-year follow-up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number., Methods: The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE-II)., Results: Forty-eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE-II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2-4 years, 5-11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE-2 increased significantly in patients younger than 2 years at treatment. In a mixed-model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not., Conclusions: Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Vascular graft and endograft infection (VGEI) is a severe complication associated with high mortality and is often challenging to diagnose. For the definitive microbiological diagnosis, sonication of vascular grafts may increase the microbiological yield of these biofilm-associated infections. The objective of this study was to determine whether sonication of explanted vascular grafts and endografts results in a higher diagnostic accuracy than conventional culture methods and aids in clinical decision-making. A prospective diagnostic study was performed comparing conventional culture with sonication culture of explanted vascular grafts in patients treated for VGEI. Explanted (endo)grafts were cut in halves and were either subjected to sonication or conventional culture. Criteria based on the Management of Aortic Graft Infection Collaboration (MAGIC) case definition of VGEI were used for definitive diagnosis. The relevance of sonication cultures was assessed by expert opinion to determine the clinical impact on decision-making. Fifty-seven vascular (endo)graft samples from 36 patients (four reoperations; 40 episodes) treated for VGEI were included; 32 episodes were diagnosed with VGEI. Both methods showed a positive culture in 81% of the cases. However, sonication culture detected clinically relevant microorganisms that went unnoticed by conventional culturing in 9 out of 57 samples (16%, 8 episodes) and provided additional relevant information regarding growth densities in another 11 samples (19%, 10 episodes). Sonication of explanted vascular grafts and endografts improves the microbiological yield and aids in the clinical decision-making for patients with a suspected VGEI compared to conventional culture alone. IMPORTANCE Sonication culture of explanted vascular grafts was shown to be a noninferior method compared to conventional culturing in diagnosing vascular graft and endograft infection (VGEI). Moreover, sonication culture has probable additional value in microbiological characterization of VGEI by giving more detailed information on growth densities, especially when the conventional culture shows intermediate growth. In this prospective design, for the first time, a direct comparison is made between sonication culturing and conventional culturing in VGEI, while taking clinical interpretation into account. Therefore, this study is another step toward a more accurate microbiological diagnosis of VGEI, influencing clinical decision-making.

Marine macroalgae are considered an untapped source of healthy natural metabolites and their market demand is rapidly increasing. Intertidal macroalgae present chemical defense mechanisms that enable them to thrive under changing environmental conditions. These intracellular chemicals include compounds that can be used for human benefit. The aim of this study was to test cultivation protocols that direct seaweed metabolic responses to enhance the production of target antioxidant and photoprotective biomaterials. We present an original integrated multi-trophic aquaculture (IMTA) design, based on a two-phase cultivation plan, in which three seaweed species were initially fed by fish effluents, and subsequently exposed to various abiotic stresses, namely, high irradiance, nutrient starvation, and high salinity. The combined effect of the IMTA's high nutrient concentrations and/or followed by the abiotic stressors enhanced the seaweeds' content of mycosporine-like amino acids (MAAs) by 2.3-fold, phenolic compounds by 1.4-fold, and their antioxidant capacity by 1.8-fold. The Sun Protection Factor (SPF) rose by 2.7-fold, and the chlorophyll and phycobiliprotein synthesis was stimulated dramatically by an order of magnitude. Our integrated cultivation system design offers a sustainable approach, with the potential to be adopted by emerging industries for food and health applications.

Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits glycolysis in NK cells. However, acute treatment with the inhibitor has no effect on NK cell effector functions. Prolonged inhibition of glucose uptake by Glutor prevents the proliferation of NK cells, increases their pro-inflammatory regulatory function and reduces the stimulation-dependent production of IFN-γ. Interestingly, even after prolonged Glutor treatment NK cell cytotoxicity and serial killing activity were still intact, demonstrating that cytotoxic NK cell effector functions are remarkably robust against metabolic disturbances.

Type I interferons (IFNs) present the first line of defense against viral infections, providing antiviral, immunomodulatory and antiproliferative effects. The type I IFN family contains 12 IFNα subtypes and IFNβ, and although they share the same receptor, they are classified as non-redundant, capable to induce a variety of different IFN-stimulated genes. However, the biological impact of individual subtypes remains controversial. Recent data propose a subtype-specificity of type I IFNs revealing unique effector functions for different viruses and thus expanding the implications for IFNα-based antiviral immunotherapies. Despite extensive research, drug-resistant infections with herpes simplex virus type 1 (HSV-1), which is the common agent of recurrent orogenital lesions, are still lacking a protective or curing therapeutic. However, due to the risk of generalized infections in immunocompromised hosts as well as the increasing incidence of resistance to conventional antiherpetic agents, HSV infections raise major health concerns. Based on their pleiotropic effector functions, the application of type I IFNs represents a promising approach to inhibit HSV-1 replication, to improve host immunity and to further elucidate their qualitative differences. Here, selective IFNα subtypes and IFNβ were evaluated for their therapeutic potential in genital HSV-1 infections. Respective in vivo studies in mice revealed subtype-specific differences in the reduction of local viral loads. IFNβ had the strongest antiviral efficacy against genital HSV-1 infection in mice, whereas IFNα1, IFNα4, and IFNα11 had no impact on viral loads. Based on flow cytometric analyses of underlying immune responses at local and peripheral sites, these differences could be further assigned to specific modulations of the antiviral immunity early during HSV-1 infection. IFNβ led to enhanced systemic cytokine secretion and elevated cytotoxic responses, which negatively correlated with viral loads in the vaginal tract. These data provide further insights into the diversity of type I IFN effector functions and their impact on the immunological control of HSV-1 infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schmitz, Schwerdtfeger, Westmeier, Littwitz-Salomon, Alt, Brochhagen, Krawczyk and Sutter.)

Background: Hybrid imaging (e.g., positron emission tomography [PET]/computed tomography [CT], PET/magnetic resonance imaging [MRI]) helps one to visualize and quantify morphological and physiological tumor characteristics in a single study. The noninvasive characterization of tumor heterogeneity is essential for grading, treatment planning, and following-up oncological patients. However, conventional (CONV) image-based parameters, such as tumor diameter, tumor volume, and radiotracer activity uptake, are insufficient to describe tumor heterogeneities. Here, radiomics shows promise for a better characterization of tumors. Nevertheless, the validation of such methods demands imaging objects capable of reflecting heterogeneities in multi-modality imaging. We propose a phantom to simulate tumor heterogeneity repeatably in PET, CT, and MRI., Methods: The phantom consists of three 50-ml plastic tubes filled partially with acrylic spheres of S1: 1.6 mm, S2: 50%(1.6 mm)/50%(6.3 mm), or S3: 6.3-mm diameter. The spheres were fixed to the bottom of each tube by a plastic grid, yielding one sphere free homogeneous region and one heterogeneous (S1, S2, or S3) region per tube. A 3-tube phantom and its replica were filled with a fluorodeoxyglucose (18F) solution for test-retest measurements in a PET/CT Siemens TPTV and a PET/MR Siemens Biograph mMR system. A number of 42 radiomic features (10 first order and 32 texture features) were calculated for each phantom region and imaging modality. Radiomic features stability was evaluated through coefficients of variation (COV) across phantoms and scans for PET, CT, and MRI. Further, the Wilcoxon test was used to assess the capability of stable features to discriminate the simulated phantom regions., Results: The different patterns (S1-S3) did present visible heterogeneity in all imaging modalities. However, only for CT and MRI, a clear visual difference was present between the different patterns. Across all phantom regions in PET, CT, and MR images, 10, 16, and 21 features out of 42 evaluated features in total had a COV of 10% or less. In particular, CONV, histogram, and gray-level run length matrix features showed high repeatability for all the phantom regions and imaging modalities. Several of repeatable texture features allowed the image-based discrimination of the different phantom regions (p < 0.05). However, depending on the feature, different pattern discrimination capabilities were found for the different imaging modalities., Conclusion: The proposed phantom appears suitable for simulating heterogeneities in PET, CT, and MRI. We demonstrate that it is possible to select radiomic features for the readout of the phantom. Most of these features had been shown to be relevant in previous clinical studies., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Concrete Outdoor Runs (OUTRUNs) are a characteristic part of organic pig housing. They must allow species-specific behaviours such as rooting and elimination, as explicitly required by organic legislation of the European Union (EU). However, OUTRUN design often fails to fulfil behavioural needs, and excreta can cover large parts of the OUTRUN leading to poor pen hygiene and associated ammonia (NH 3 ) emissions. This review integrates legislative, ethological and environmental requirements for OUTRUNs for organic growing-finishing pigs. While EU regulations specify some welfare-related standards for OUTRUNs (e.g. minimal space allowance), national and private standards interpret some aspects differently, e.g. the proportion of roofed and slatted floor area. Furthermore, reducing NH 3 emissions is equally a challenge for organic systems, even though EU legislation does not explicitly refer to OUTRUNs. Depending on the actual use of the OUTRUN for elimination, higher space allowance compared to conventional production norms increases the potential for a large NH 3 -emitting surface. The design of pen features (e.g. roof, floor, enrichment) can encourage pigs to separate functional areas and consequently reduce the elimination area and associated NH 3 emissions. While providing the main lying area indoors, resting outdoors should be possible for sub-groups during the day. A roof protects pigs and resources (e.g. bedding) from adverse weather, but the effect on pig welfare and NH 3 emissions is site-specific. A floor design that ensures practicable manure removal and drainage is most important to reduce emissions. Providing opportunities for exploring and rooting in the OUTRUN has particular relevance for pigs' behavioural needs and can improve pen hygiene by reducing the elimination area. Cooling facilities are increasingly important to prevent heat stress and its detrimental effects on welfare and pen hygiene. Finally, practicability for farmers needs to be ensured for all resources provided in OUTRUNs, as good management is crucial. Research gaps emerge regarding the association between soiling and NH 3 and the influence of certain pen features (shape, roof, feeder location, pen partitions and wet areas) on pig behaviour and soiling., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

It remains controversial how interferon (IFN) response contributes to hepatitis B virus (HBV) control and pathogenesis. A previous study identified that hydrodynamic injection (HI) of type I IFN (IFN-I) inducer polyinosinic-poly(C) [poly(I·C)] leads to HBV clearance in a chronic HBV mouse model. However, recent studies have suggested that premature IFN-I activation in the liver may facilitate HBV persistence. In the present study, we investigated how the early IFN-I response induces an immunosuppressive signaling cascade and thus causes HBV persistence. We performed HI of the plasmid adeno-associated virus (pAAV)/HBV1.2 into adult BALB/c mice to establish an adult acute HBV replication model. Activation of the IFN-I signaling pathway following poly(I·C) stimulation or murine cytomegalovirus (MCMV) infection resulted in subsequent HBV persistence. HI of poly(I·C) with the pAAV/HBV1.2 plasmid resulted in not only the production of IFN-I and the anti-inflammatory cytokine interleukin-10 (IL-10) but also the expansion of intrahepatic regulatory T cells (Tregs), Kupffer cells (KCs), and myeloid-derived suppressor cells (MDSCs), all of which impaired the T cell response. However, when poly(I·C) was injected at day 14 after the HBV plasmid injection, it significantly enhanced HBV-specific T cell responses. In addition, interferon-alpha/beta receptor (IFNAR) blockade rescued T cell response by downregulating IL-10 expression and decreasing Treg and KC expansion. Consistently, Treg depletion or IL-10 blockade also controlled HBV replication. IMPORTANCE IFN-I plays a double-edged sword role during chronic HBV infection. Here, we identified that application of IFN-I at different time points causes contrast outcomes. Activation of the IFN-I pathway before HBV replication induces an immunosuppressive signaling cascade in the liver and consequently caused HBV persistence, while IFN-I activation post HBV infection enhances HBV-specific T cell responses and thus promotes HBV clearance. This result provided an important clue to the mechanism of HBV persistence in adult individuals.

Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity. Here, using the Friend retrovirus mouse model, we show that following infection NK cells increase nutrient uptake, including amino acids and iron, and reprogram their metabolic machinery by increasing glycolysis and mitochondrial metabolism. Specific deletion of the amino acid transporter Slc7a5 has only discrete effects on NK cells, but iron deficiency profoundly impaires NK cell antiviral functions, leading to increased viral loads. Our study thus shows the requirement of nutrients and metabolism for the antiviral activity of NK cells, and has important implications for viral infections associated with altered iron levels such as HIV and SARS-CoV-2., (© 2021. The Author(s).)

Bloodstream infections (BSIs) among older patients are frequent with high rate of mortality. Infections with multidrug-resistant organisms (MDRO) are associated with higher mortality than with susceptible microorganisms. We aimed to evaluate the prevalence of MDRO infection during BSI in older population and the factors associated with unfavorable outcome. This study is a retrospective cohort of all BSI episodes occurring among older patients (> 65yo), from April 1, 2010, to December 31, 2016, in a French university hospital for geriatric medicine. A total of 255 BSI episodes were analyzed. Mean age was 86.3±6.5 years, and sex ratio (M/F) was 0.96. Main comorbidities were orthopedic device (26.7%), active neoplasia (24.3%), and diabetes mellitus (18.4%). Main primary sites of infection were urinary tract infections (56.9%), respiratory tract infections (10.6%), intra-abdominal infections (7.1%), and skin and soft tissue infections (4.7%). Main bacteria identified were Escherichia coli (45.1%), Staphylococcus aureus (14.1%), enterococci (10.7%), coagulase-negative staphylococci (CoNS) (5.5%), and streptococci (5.1%). MDROs were involved in 17.2% of BSI (gram-negative bacilli: 9.0%; CoNS: 4.3%; and methicillin-resistant S. aureus (MRSA): 3.9%). The main factor associated with MDRO BSI was colonization with MDRO (OR=6.29; 95%CI=2.9-14.32). Total mortality was 18.4% and significantly higher in case of initial severity (OR=3.83; 95%CI=1.75-8.38), healthcare-associated infection (OR=5.29; 95%CI=1.11-25.30), and MRSA BSI (OR=9.16; 95%CI=1.67-50.16). BSI due to MDRO is frequent in older population and is strongly associated with carriage of MDRO. Healthcare-associated BSI, severe episodes, and BSI due to MRSA are associated with unfavorable outcome. In these cases, a broad-spectrum antibiotic should be promptly initiated., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) are two novel antibacterials with known efficacy against Gram-negative bacteria (GNB). We aimed to describe the efficacy and safety of surgical management combined with C/A or C/T treatment for bone and joint infections (BJIs)., Methods: We conducted an observational, bicentric study of patients treated with C/A or C/T for a BJI between May 2016 and June 2019. Failure was defined as the need for unplanned additional antibiotic treatment or orthopaedic surgery, or death due to the BJI up to the patient's latest visit., Results: Overall, 15 patients were included. Nine patients were treated with C/A, mainly for polymicrobial BJI due to multidrug-resistant (MDR) bacteria (Enterobacteriaceae, n = 7). Six patients were male, the median age was 66 years and the median Charlson comorbidity index (CCI) was 5. It was the first septic episode at the site in 3/9 patients. The cure rate was 7/9 (median follow-up, 272 days). Two patients showed C/A-related confusion. Five patients were treated with C/T for BJI involving MDR Pseudomonas aeruginosa. Four patients were male, the median age was 53 years and the median CCI was 2. All patients had previous septic episodes at the infection site. The cure rate was 3/5 (median follow-up, 350 days). One patient was successfully treated by C/T then C/A for multistage spondylodiscitis., Conclusion: In our experience, C/A and C/T are two effective and safe options, even as salvage treatment for BJI due to MDR-GNB despite the absence of label, however more data are warranted., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pancreatic surgery is associated with high morbidity, mainly due to infectious complications, so many centres use postoperative antibiotics (ATBpo) for all patients. However, antibiotic regimens vary according to local practices. The aims of this study were to describe the occurrence of surgical site infection (SSI) and ATBpo prescription after pancreatic surgery, and to determine the risk factors of postoperative SSI, in order to better define the clinical indications for ATBpo in this context., Patients and Methods: All patients undergoing scheduled major pancreatic surgery from January 2007 to November 2018 were included in this retrospective study. Patients were classified into four groups according to SSI and routine ATBpo prescription: SSI+/ATBpo+, SSI-/ATBpo+, SSI+/ATBpo- and SSI-/ATBpo-. In addition, risk factors (fever and pre-operative biliary prosthesis) associated with the occurrence of SSI and ATBpo were analysed using a logistic regression model., Results: Data from 149 patients (115 pancreaticoduodenectomies and 34 splenopancreatectomies) were analysed. Thirty (20.1%) patients experienced SSI and 42 (28.2%) received ATBpo. No difference was found in routine ATBpo prescription between patients with and without SSI (26.7% vs 28.6%, respectively; P=0.9). Amongst the 107 patients who did not receive routine ATBpo, 85 (79.4%) did not develop an SSI. In-hospital mortality did not differ between infected and uninfected patients (7% vs 2%, respectively; P=0.13). The occurrence of postoperative fever differed between SSI+ and SSI- patients (73.3% vs 34.2%, respectively; P<0.001), while the prevalence of pre-operative biliary prosthesis was similar (37.9% vs 26.7%, respectively; P=0.3)., Conclusion: Non-routine ATBpo after major pancreatic surgery resulted in 85 (56%) patients being spared unnecessary antibiotic treatment. This suggests that routine ATBpo prescription could be excessive, but further studies are needed to confirm such antibiotic stewardship. Fever appears to be a relevant clinical sign for individual-based prescription, but the presence of a biliary prosthesis does not., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Limited data have been reported regarding osteomyelitis due to carbapenemase-producing Enterobacteriaceae (CPE), including co-infections with extended-spectrum β-lactamase (ESBL)-producing micro-organisms., Methods: We conducted a retrospective study in a reference centre for bone and joint infections from 2011 to 2019 among patients infected with CPE., Results: Nine patients (mean age 46.8 ± 16.6 years), including three with infected implants, were identified. Infections were mostly polymicrobial (n = 8/9), including Staphylococcus aureus (n = 6/9). CPE were mainly OXA-48-type, associated with ESBL-producing Enterobacteriaceae (n = 8/9), of which 5/9 isolates were Klebsiella pneumoniae. Control of the infection was achieved in seven cases., Conclusions: CPE osteomyelitides are essentially polymicrobial and fluoroquinolone-resistant infections, highlighting the need for efficient surgery with implant removal., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Preoperative synovial fluid culture is pivotal in the early diagnosis of prosthetic joint infection (PJI) but may yield false-positive and false-negative results. We evaluated the predictive value of synovial fluid culture results combined with the measurement of serum anti-staphylococcal antibodies (SASA)., Questions/purposes: (1) For hip and knee PJI, does combining positive SASA results with preoperative synovial culture results improve the positive predictive value (PPV) of preoperative synovial fluid culture alone? (2) Does combining preoperative synovial fluid culture results with a positive cell count and differential result increase the PPV of preoperative synovial fluid culture alone? (3) What proportion of isolated organisms exhibit concordance in antibiotic susceptibility: preoperative aspiration versus intraoperative isolates?, Methods: A prospective study was conducted at two French reference centers that manage bone and joint infections and included 481 adult patients who had a revision or resection arthroplasty between June 25, 2012 and June 23, 2014. Exclusion criteria including no serum sample available for immunoassay, the lack of microbiological documentation, and the absence of preoperative aspiration reduced the patient number to 353. Seven patients with an undetermined SASA result were excluded from the analysis. We also excluded patients with PJI involving more than one Staphylococcus species (polystaphylococcal infection) and those in whom more than one Staphylococcus species was recovered from the preoperative synovial fluid culture (polystaphylococcal synovial fluid culture). In total, 340 patients were included in the analysis (no infection, 67% [226 of 340]; staphylococcal infection, 21% [71 of 340]; other infection, 13% [43 of 340]). The preoperative synovial fluid analysis included a cell count and differential and bacterial culture. SASAs were measured using a multiplex immunoassay. The diagnosis of PJI was determined using the Infectious Diseases Society of America (IDSA) criteria [] and intraoperative tissue culture at the time of revision surgery was used as the gold standard (at least one positive intraoperative sample for a "virulent" organism (such as S. aureus) or two positive samples for a "non-virulent" (for example S. epidermidis)., Results: SASA increased the PPV compared with synovial fluid culture alone (92% [95% CI 82 to 97] versus 79% [95% CI 68 to 87]; p = 0.04); when stratified by site, an increase in PPV was seen in hip infections (100% [95% CI 89 to 100] versus 77% [95% CI 63 to 88]; p = 0.01) but not in knee infections (84% [95% CI 66 to 95] versus 80% [95% CI 64 to 91]; p = 0.75). A positive cell count and differential result increased the PPV of staphylococcal synovial fluid cultures compared with synovial fluid culture alone (86% [95% CI 70 to 95] versus 79% [95% CI 68 to 87]; p = 0.36); when stratified by site, no difference in hip and knee infections was observed (86% [95% CI 67 to 96] versus 77% [95% CI 63 to 88]; p = 0.42) and 86% [95% CI 70 to 95] versus 80% [95% CI 64 to 91]; p = 0.74)., Conclusion: SASA measurement improves the predictive value of synovial fluid cultures of the hip for all staphylococcal organisms, including coagulase-negative staphylococci, but the PPV of SASA plus synovial fluid culture it is not superior to the PPV of synovial fluid cell count/differential plus synovial culture for the knee., Level of Evidence: Level III, diagnostic study.