[Prognostic factors of extracorporeal membrane oxygenation in the treatment of severe pediatric acute respiratory distress syndrome].

Objective: To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support. Methods: It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results: Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO2/FiO2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH2O (1 cmH2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis (P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO (P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO (P<0.05) and gradually increased from 24 h after ECMO. Conclusions: The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

Predictive modeling of perioperative patient deterioration: combining unanticipated ICU admissions and mortality for improved risk prediction.

OBJECTIVE: This paper presents a comprehensive analysis of perioperative patient deterioration by developing predictive models that evaluate unanticipated ICU admissions and in-hospital mortality both as distinct and combined outcomes. MATERIALS AND METHODS: With less than 1% of cases resulting in at least one of these outcomes, we investigated 98 features to identify their role in predicting patient deterioration, using univariate analyses. Additionally, multivariate analyses were performed by employing logistic regression (LR) with LASSO regularization. We also assessed classification models, including non-linear classifiers like Support Vector Machines, Random Forest, and XGBoost. RESULTS: During evaluation, careful attention was paid to the data imbalance therefore multiple evaluation metrics were used, which are less sensitive to imbalance. These metrics included the area under the receiver operating characteristics, precision-recall and kappa curves, and the precision, sensitivity, kappa, and F1-score. Combining unanticipated ICU admissions and mortality into a single outcome improved predictive performance overall. However, this led to reduced accuracy in predicting individual forms of deterioration, with LR showing the best performance for the combined prediction. DISCUSSION: The study underscores the significance of specific perioperative features in predicting patient deterioration, especially revealed by univariate analysis. Importantly, interpretable models like logistic regression outperformed complex classifiers, suggesting their practicality. Especially, when combined in an ensemble model for predicting multiple forms of deterioration. These findings were mostly limited by the large imbalance in data as post-operative deterioration is a rare occurrence. Future research should therefore focus on capturing more deterioration events and possibly extending validation to multi-center studies. CONCLUSIONS: This work demonstrates the potential for accurate prediction of perioperative patient deterioration, highlighting the importance of several perioperative features and the practicality of interpretable models like logistic regression, and ensemble models for the prediction of several outcome types. In future clinical practice these data-driven prediction models might form the basis for post-operative risk stratification by providing an evidence-based assessment of risk.

[Characteristics of liver volume and pathological changes with different stages of liver fibrosis in chronic liver disease].

Objective: To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature, hepatocyte apoptosis, and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease. Methods: 53 patients with chronic hepatitis B, alcoholic fatty liver disease, autoimmune liver disease, nonalcoholic fatty liver disease, and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected. Patients were divided into early (F1-2), middle (F3-4), and late (F5-6) in accordance with the Ishak fibrosis stage and Masson stain. The liver and spleen volumes were measured using ITK-SNAP software. CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis. Ki67 and HNF-4α multiplex immunohistochemical staining were used to reflect hepatocyte regeneration. GS staining was used to determine parenchymal extinction lesions. TUNEL staining was used to observe hepatocyte apoptosis. Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes. Results: As liver fibrosis progressed, the total liver volume and right lobe liver volume gradually decreased (P<0.05), while the spleen volume gradually increased (P<0.05). The expression of CD31 and GS gradually increased (P<0.05), and the expression of Ki67 first increased and then decreased (P<0.05). The positivity rate of CD31 was negatively correlated with the right lobe liver volume (r=-0.609, P<0.001) and the total liver volume (r=-0.363, P=0.017). The positivity rate of Ki67 was positively correlated with the right lobe liver volume (r=0.423, P=0.018), while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume (r=-0.860, P<0.001). The positivity rate of GS was negatively correlated with the right lobe liver volume (r=-0.440, P=0.002), and the number of PELs was negatively correlated with RV (r=-0.476, P=0.013). The CD31 positive staining area was negatively correlated with the Ki67 positive staining area(r=-0.511, P=0.009). Conclusion: As liver fibrosis progresses, patients with chronic liver disease have a depletion in total liver volume and right lobe liver volume, and this is mainly in correlation with fewer liver cells and liver tissue microvasculature disorders.

Deepvirusclassifier: a deep learning tool for classifying SARS-CoV-2 based on viral subtypes within the coronaviridae family.

PURPOSE: In this study, we present DeepVirusClassifier, a tool capable of accurately classifying Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral sequences among other subtypes of the coronaviridae family. This classification is achieved through a deep neural network model that relies on convolutional neural networks (CNNs). Since viruses within the same family share similar genetic and structural characteristics, the classification process becomes more challenging, necessitating more robust models. With the rapid evolution of viral genomes and the increasing need for timely classification, we aimed to provide a robust and efficient tool that could increase the accuracy of viral identification and classification processes. Contribute to advancing research in viral genomics and assist in surveilling emerging viral strains. METHODS: Based on a one-dimensional deep CNN, the proposed tool is capable of training and testing on the Coronaviridae family, including SARS-CoV-2. Our model's performance was assessed using various metrics, including F1-score and AUROC. Additionally, artificial mutation tests were conducted to evaluate the model's generalization ability across sequence variations. We also used the BLAST algorithm and conducted comprehensive processing time analyses for comparison. RESULTS: DeepVirusClassifier demonstrated exceptional performance across several evaluation metrics in the training and testing phases. Indicating its robust learning capacity. Notably, during testing on more than 10,000 viral sequences, the model exhibited a more than 99% sensitivity for sequences with fewer than 2000 mutations. The tool achieves superior accuracy and significantly reduced processing times compared to the Basic Local Alignment Search Tool algorithm. Furthermore, the results appear more reliable than the work discussed in the text, indicating that the tool has great potential to revolutionize viral genomic research. CONCLUSION: DeepVirusClassifier is a powerful tool for accurately classifying viral sequences, specifically focusing on SARS-CoV-2 and other subtypes within the Coronaviridae family. The superiority of our model becomes evident through rigorous evaluation and comparison with existing methods. Introducing artificial mutations into the sequences demonstrates the tool's ability to identify variations and significantly contributes to viral classification and genomic research. As viral surveillance becomes increasingly critical, our model holds promise in aiding rapid and accurate identification of emerging viral strains.

Assessment of the chemical composition of buriti (Mauritia flexuosa Liliopsida) and cassava (Manihot esculenta Crantz) residues and their possible application in the bioproduction of coconut aroma (6 pentyl-α-pyrone).

This work aimed to define strategies to increase the bioproduction of 6 pentyl-α-pyrone (bioaroma). As first strategy, fermentations were carried out in the solid state, with agro-industrial residues: Mauritia flexuosa Liliopsida. and Manihot esculenta Crantz in isolation, conducting them with different nutrient solutions having Trichoderma harzianum as a fermenting fungus. Physicochemical characterizations, centesimal composition, lignocellulosic and mineral content and antimicrobial activity were required. Fermentations were conducted under different humidification conditions (water, nutrient solution without additives and nutrient solutions with glucose or sucrose) for 9 days. Bioaroma was quantified by gas chromatography, assisted by solid-phase microextraction. The results showed the low production of this compound in fermentations conducted with sweet cassava (around 6 ppm (w/w)). The low bioproduction with sweet cassava residues can probably be related to its starch-rich composition, homogeneous substrate, and low concentration of nutrients. Already using buriti, the absence of aroma production was detected. Probably the presence of silicon and high lignin content in buriti minimized the fungal activity, making it difficult to obtain the aroma of interest. Given the characteristics presented by the waste, a new strategy was chosen: mixing waste in a 1:1 ratio. This fermentation resulted in the production of 156.24 ppm (w/w) of aroma using the nutrient solution added with glucose. This combination, therefore, promoted more favorable environment for the process, possibly due to the presence of fermentable sugars from sweet cassava and fatty acids from the buriti peel, thus proving the possibility of an increase of around 2500% in the bioproduction of coconut aroma.

Extracellular matrix modulates depot-specific adipogenic capacity in adipose tissue of dairy cattle.

Adipose tissue (AT) expands through both hyperplasia and hypertrophy. During adipogenesis, adipose stromal and progenitor cells (ASPCs) proliferate and then accumulate lipids, influenced by the local AT microenvironment. Increased adipogenic capacity is desirable as it relates to metabolic health, especially in transition dairy cows where excess free fatty acids in circulation can compromise metabolic and immune health. Our aim was to elucidate the depot-specific adipogenic capacity and ECM properties of subcutaneous (SAT) and visceral (VAT) AT of dairy cows and define how the ECM affects adipogenesis. Flank SAT and omental VAT samples were collected from dairy cows in a local abattoir. Tissue samples were utilized for transcriptome analysis, targeted RT-qPCR for adipogenic markers, adipocyte sizing, assessment of viscoelastic properties and collagen accumulation, and then decellularized for native ECM isolation. For in vitro analyses, SAT and VAT samples were digested via collagenase, and ASPCs cultured for metabolic analysis. Adipogenic capacity was assessed by adipocyte size, quantification of ASPCs in stromal vascular fraction (SVF) via flow cytometry, and gene expression of adipogenic markers. In addition, functional assays including lipolysis and glucose uptake were performed to further characterize SAT and VAT adipocyte metabolic function. Data were analyzed using SAS (version 9.4; SAS institute Inc., Cary, NC) and GraphPad Prism 9. Subcutaneous AT adipogenic capacity was greater than VAT's, as indicated by increased ASPCs abundance, increased magnitude of adipocyte ADIPOQ and FASN expression during differentiation, and higher adipocyte lipid accumulation as shown by an increased proportion of larger adipocytes and abundance of lipid droplets. Rheologic analysis revealed that VAT is stiffer than SAT, which led us to hypothesize that differences between SAT and VAT adipogenic capacity were partly mediated by depot-specific ECM microenvironment. Thus, we studied depot-specific ECM-adipocyte crosstalk using a 3D model with native ECM (decellularized AT). Subcutaneous AT and VAT ASPCs were cultured and differentiated into adipocytes within depot-matched and mis-matched ECM for 14d, followed by ADIPOQ expression analysis. Visceral AT ECM impaired ADIPOQ expression in SAT cells. Our results demonstrate that SAT is more adipogenic than VAT and suggest that divergences between SAT and VAT adipogenesis are partially mediated by the depot-specific ECM microenvironment.

[Brainstem auditory evoked responses in horses with hearing loss and during general anesthesia]. / Hör- und Hirnstammfunktionsprüfung beim Pferd: Resultate bei ausgewählten klinischen Szenarien.

INTRODUCTION: The brainstem auditory evoked response (BAER) is a diagnostic approach to examine the hearing system of horses objectively. The aim of this BAER examination was the diagnosis of conductive or sensorineural hearing loss or deafness in horses with external otitis, head trauma, headshaking, tinnitus or skittish horses with eye disease. Brainstem dysfunction is induced by intracranial hypotension. BAER was used in horses with colic surgery which had a low arterial blood pressure during general anesthesia. The endoscopic finding of the guttural pouch was the ipsilateral mild to severe hypertrophy of the tympanostylohyoideum in horses with external otitis or head trauma. The otoscopic examination of standing sedated horses was done before BAER. The cartilagineous and osseous part of the external ear canal in horses with external otitis were obstructed with exsudate and tympanic membranes were not visible. Horses with right sided external otitis: right moderate to severe conductive hearing loss (significantly prolonged latencies of I, III, V and interpeak latencies I-III, I-V, III-V; thresholds of hearing levels 60 to 80 dB right); horses with left sided external otitis: left severe conductive hearing loss (no correct identification of BAER peaks, latencies not measurable, 80 dB); horse with left sided head trauma: severe left sided conductive hearing loss (blood in the left external ear canal, no visible tympanic membrane, no correct identification of BAER peaks, latencies not measurable, 80 dB); horses with head shaking: mild sensorineural hearing loss on both sides (on both sides osseous parts II/III with keratin scales of the junction, visible tympanic membranes, significantly prolonged V, I-III, I-V, 40 dB); moderate to severe skittish horses with chronic eye disease (mostly left sided equine recurrent uveitis): moderate sensorineural hearing loss on both sides (normal otoscopical findings, significantly prolonged latencies and interpeak latencies left; I-V, III-V right, 60 dB, pathological involvement in the auditory pathway of the brainstem between the cochlear nucleus and colliculus caudalis); horse with a tinnitus on both sides: mild sensorineural hearing loss on both sides (normal otoscopical findings, prolonged V, I-III, I-V, III-V, 40 dB, pathology of auditory nerve, cochlear nucleus and above the level of this nucleus); American paint horses: sensorineurale deafness on both sides (normal otoscopical findings, absent BAER peaks, isoelectric lines and 80 dB on both sides). The prolonged latencies of I, III and V including interpeak latencies I-III only left and I-V and III-V on both sides in horses with laparotomy during general anesthesia were associated with low arterial blood pressure (62 mmHg, median). These findings could demonstrate a hypotension in the brainstem too. The BAER could be a technical tool during general anesthesia for normalizing the arterial blood pressure and brainstem function to prevent imbalance of body movements after general anesthesia.

INTRODUCTION: L'examen objectif de l'audition chez le cheval est réalisé par la mesure des Potentiels Évoqués Auditifs (PEA) ou Brainstem Auditory-Evoked Response (BAER). L'objectif de ces examens est de diagnostiquer une surdité de transmission ou neurosensorielle ou une surdité chez les chevaux souffrant d'otite externe, de traumatisme crânien, de headshaking, d'acouphènes ou chez des chevaux craintifs souffrant d'une maladie oculaire. Étant donné que l'audiométrie du tronc cérébral vérifie également la fonction du tronc cérébral, des chevaux ayant subi une laparotomie et une déshydratation préopératoire ont été examinés pour détecter un dysfonctionnement du tronc cérébral dû à une baisse de la pression artérielle. L'otoscopie et l'audiométrie du tronc cérébral (système AEP Corona) ont été réalisées. Les résultats de l'otoscopie chez les chevaux atteints d'otite externe: Pars cartilaginea et ossea degré III, tympan non visible. Les résultats de l'endoscopie des poches gutturales chez les chevaux atteints d'otite externe exsudative ou de traumatisme crânien: toujours une augmentation ou une hypertrophie ipsilatérale du tympanostylohyoïdien. Les résultats de la BAER des chevaux atteints d' une otite externe à droite sont les suivants: surdité de transmission moyenne à sévère à droite (ondes I, III, V significativement prolongées, latences interpicales I-III, I-V, III-V par rapport au groupe de contrôle, valeurs limites au-dessus du seuil auditif normal 60 à 80 dB); chevaux atteints d'otite externe à gauche: surdité de transmission de haut niveau à gauche (ondes non identifiables, 80 dB à gauche); chevaux avec une fistule auriculaire à droite: surdité de perception bilatérale de bas niveau (allongement significatif des ondes III, V et des latences interpicales des deux côtés, 40 dB); cheval avec traumatisme crânien à gauche: surdité de transmission de degré élevé (à gauche, sang dans le conduit auditif externe, tympan non visible, ondes non identifiables, 80 dB); chevaux avec headshaking: surdité de perception de degré faible (des deux côtés, pars ossea de degré II, tympans visibles, allongement significatif V, I-III, I-V, 40 dB); chevaux présentant une peur et une maladie oculaire: surdité moyenne, neurosensorielle (otoscopie normale, allongement significatif de toutes les ondes et des latences interpeak à gauche, I-V, III-V à droite, 60 dB, vitesse pathologique de conduction des voies auditives dans le tronc cérébral); American Paint Horses: surdité neurosensorielle (otoscopie normale, ligne isoélectrique bilatérale des HA, 80 dB). Les ondes I, III et V prolongées et les latences interpicales I-III, I-V et III-V chez les chevaux ayant subi une laparotomie sont associées à la baisse de la pression artérielle (62 mmHg, médiane) pendant l'anesthésie générale et indiquent une hypotension dans le tronc cérébral. Pendant l'anesthésie générale, l'audiométrie du tronc cérébral offre une possibilité particulière de détecter le dysfonctionnement du tronc cérébral, de réguler la pression artérielle et de garantir un lever sans problème avec un équilibre auditif et visuel de la posture après l'anesthésie générale.

Study of a Subcutaneous Lesion of the Shoulder: The Saint Paolino Tumor.

In certain small counties in southern Italy, traditional Catholic festivals are observed by erecting tall, large, and weighty wagons referred to as "lilies." These wagons are borne on the shoulders of several individuals known as "cradles." This practice has given rise to the emergence of a distinct subcutaneous neoformation on the shoulder. This study investigates the unique clinical and anatomopathological attributes of "Saint Paolino tumor" (named in honor of the Catholic patron of the widely celebrated lilies festival). This tumor presents as a posttraumatic intermittent chronic lesion occurring on the shoulder, necessitating differential diagnosis from other cutaneous and soft tissue lesions such as spontaneous lipomas, elastofibroma, Madelung disease, and liposarcoma.

Right trace wrong place: a normal capnography trace despite the tip of the tracheal tube existing outside the airway.

Head and neck trauma can result in difficult airway management. A 25-year-old male required emergency tracheal intubation on arrival to the emergency department following a motorbike accident. Despite the presence of a normal capnography a computed tomography scan demonstrated a tracheal opening, an extra-tracheal position of the distal end of the tracheal tube, and extensive subcutaneous emphysema. The tube was re-directed into the trachea and the tracheal injury was surgically repaired. This case highlights that the presence of a normal capnograph does not necessarily mean that the distal end of the tracheal tube resides within the airway.

High variability in assays of blood markers of collagen turnover in cardiovascular disease: Implications for research and clinical practice.

AIMS: Fibrosis is a common feature of many chronic diseases, including heart failure, which can have deleterious effects on cardiac structure and function that are associated with adverse outcomes. By-products of collagen synthesis and degradation, such as carboxy- and amino-terminal pro- or telo-peptides of collagen type I and III (PICP, PINP, PIIINP, and CITP) have been extensively investigated as markers of fibrosis. Although the majority of studies report on the reproducibility of their assay results, there is no a comparison of biomarker assays across studies. Therefore, we conducted a systematic review adhering to PRISMA guidelines. METHODS AND RESULTS: The search terms employed in Medline were: 'collagen AND cardiac' or 'collagen AND heart'. This query yielded a total of 1049 articles. Thereafter, specific search criteria were applied: (i) original English-language papers; (ii) human studies; (iii) in-vivo investigations; and (iv) blood/serum/plasma samples. Overall, 89 studies were identified (42 on PIIINP, 32 on PICP, 29 on CITP, and 17 on PINP). The range of reported values for PIIINP was between 0.06 to 11 800 µg/l; for PICP 0.006 to 1265 µg/l; for CITP 0.3 to 5450 µg/l; for PINP 0.15 to 80 µg/l. Extreme variations in values for fibrosis biomarkers were observed across studies, especially when different assays were used, but also with the same assays. CONCLUSIONS: Our findings show that it is challenging to ascertain normal ranges or compare studies for the measurement of fibrosis biomarkers. Given the potential implications for clinical practice and current lack of awareness of these issues, this subject warrants comprehensive acknowledgement and understanding.

Deriving Automated Device Metadata From Intracranial Pressure Waveforms: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury ICU Physiology Cohort Analysis.

IMPORTANCE: Treatment for intracranial pressure (ICP) has been increasingly informed by machine learning (ML)-derived ICP waveform characteristics. There are gaps, however, in understanding how ICP monitor type may bias waveform characteristics used for these predictive tools since differences between external ventricular drain (EVD) and intraparenchymal monitor (IPM)-derived waveforms have not been well accounted for. OBJECTIVES: We sought to develop a proof-of-concept ML model differentiating ICP waveforms originating from an EVD or IPM. DESIGN, SETTING, AND PARTICIPANTS: We examined raw ICP waveform data from the ICU physiology cohort within the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury multicenter study. MAIN OUTCOMES AND MEASURES: Nested patient-wise five-fold cross-validation and group analysis with bagged decision trees (BDT) and linear discriminant analysis were used for feature selection and fair evaluation. Nine patients were kept as unseen hold-outs for further evaluation. RESULTS: ICP waveform data totaling 14,110 hours were included from 82 patients (EVD, 47; IPM, 26; both, 9). Mean age, Glasgow Coma Scale (GCS) total, and GCS motor score upon admission, as well as the presence and amount of midline shift, were similar between groups. The model mean area under the receiver operating characteristic curve (AU-ROC) exceeded 0.874 across all folds. In additional rigorous cluster-based subgroup analysis, targeted at testing the resilience of models to cross-validation with smaller subsets constructed to develop models in one confounder set and test them in another subset, AU-ROC exceeded 0.811. In a similar analysis using propensity score-based rather than cluster-based subgroup analysis, the mean AU-ROC exceeded 0.827. Of 842 extracted ICP features, 62 were invariant within every analysis, representing the most accurate and robust differences between ICP monitor types. For the nine patient hold-outs, an AU-ROC of 0.826 was obtained using BDT. CONCLUSIONS AND RELEVANCE: The developed proof-of-concept ML model identified differences in EVD- and IPM-derived ICP signals, which can provide missing contextual data for large-scale retrospective datasets, prevent bias in computational models that ingest ICP data indiscriminately, and control for confounding using our model's output as a propensity score by to adjust for the monitoring method that was clinically indicated. Furthermore, the invariant features may be leveraged as ICP features for anomaly detection.

Performance and clinical outcomes in telestroke remain robust during the COVID-pandemic: insight into the NEVAS network.

BACKGROUND: The COVID-19 pandemic had significant impact on global healthcare, including stroke management. Telemedical stroke networks have emerged with positive results for patient outcome in rural areas without stroke expertise. However, telestroke faced enormous on-site challenges during the pandemic. So far, data on performance and clinical outcomes in telestroke settings during the COVID-pandemic are scarce. METHODS: We retrospectively analyzed data from stroke patients treated in four spoke hospitals of the Bavarian telestroke network NEVAS in 2020-2021 and 2019 as reference year and compared the 3 years for various parameters. Primary outcome was functional outcome according to the modified Rankin scale (mRS). Secondary outcome parameters included time intervals, periprocedural intracranial hemorrhage rates, and mortality. RESULTS: In 2019-2021, 2820 patients were treated for acute ischemic stroke with an admission decrease of 10% during the pandemic. Of those, 241 received only IVT and 204 were transferred to our center for MT. Door-to-imaging, door-to-needle, and symptom-onset-to-groin times remained comparable in the 3 years. Complication rates remained at a low level. Good clinical outcome rates (mRS 0-2) at discharge remained stable for all stroke patients (82-84%) and for those treated with IVT (64-77%). Good clinical outcome rates at 3 month follow-up for MT patients declined in 2020 (23% vs. 35% in 2019) but recovered again in 2021 (42%). Mortality rates did not increase for all patient groups analyzed. CONCLUSIONS: Stroke care remained robust during the COVID-pandemic within our network, indicating that well-established telestroke networks can overcome unexpected critical challenges such as a pandemic, guaranteeing best practice stroke care in rural areas.

Effects of riparian vegetation restoration and environmental context on ecosystem functioning in tropical streams of southeastern Brazil.

Tropical stream ecosystems are under increasing human pressure, making the development of effective restoration approaches and expanding knowledge in this field urgent. This study evaluated the impact of riparian vegetation restoration and environmental context on stream ecosystem functioning by measuring key ecosystem functions - gross primary production (GPP), ecosystem respiration (ER), and nutrient uptake of ammonium and soluble reactive phosphorus - across ten tropical streams in southeastern Brazil. The streams represented a gradient from clearcut areas (impacted reaches) to relatively pristine conditions (reference reaches), including intermediate stages of vegetation recovery (restored reaches). In the short-term (~15-20 years after restoration), restoration led to reduced GPP akin to reference reaches. Yet, ER did not show the anticipated increase, suggesting a longer timeframe is necessary for restored streams to emulate the functional characteristics of reference reaches. Additionally, the restored reaches did not achieve the nutrient uptake efficiencies observed in both impacted and reference reaches, pointing to a partial recovery of ecosystem function. This study suggests that while riparian vegetation restoration contributes positively to certain aspects of stream function, environmental variables less related to this type of restoration, such as discharge and hydromorphology, significantly influence stream ecosystem functioning, highlighting the importance of considering environmental context in restoration efforts. A more holistic approach, possibly encompassing broader hydromorphological and habitat enhancements, is needed to fully restore ecological processes in these vital ecosystems. These insights are critical for informing future tropical stream restoration projects, advocating the use of ecosystem function metrics as comprehensive indicators of ecological recovery and restoration success.

Three New Polyprenylated Benzophenone Derivatives Isolated from Clusia burle-marxii.

Three new polyprenylated benzophenone derivatives named burlemarxione G-I (1-3) were isolated from C. burle-marxii trunks (compound 1) and leaves (compounds 2 and 3), along with the known compound burlemarxione F. Burlemarxione G (1) was isolated after methylation with diazomethane and it is the keto-enol tautomeric pair of burlemarxione F. Burlemarxione H (2) derives from burlemarxiones F and G, but it has additional rings due to cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. Burlemarxione I (3) has two additional cyclizations: the first encompasses the cyclization of the former isopentenyl group into an 11,11-dimethyl-six-membered ring, whereas the second produces additional rings due to the cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. All three compounds showed moderate anti-glioma activity. These results show that C. burle-marxii is an important source of sophisticated polyprenylated benzophenone derivatives.

QTL discovery for agronomic and quality traits in diploid potato clones using PotatoMASH amplicon sequencing.

We genotyped a population of 618 diploid potato clones derived from six independent potato-breeding programmes from NW-Europe. The diploids were phenotyped for 23 traits, using standardised protocols and common check varieties, enabling us to derive whole population estimators for most traits. We subsequently performed a Genome-Wide Association Study (GWAS) to identify quantitative trait loci (QTL) for all traits with SNPs and short-read haplotypes derived from read-backed phasing. In this study, we used a marker platform called PotatoMASH (Potato Multi-Allele Scanning Haplotags); a pooled multiplex amplicon sequencing based approach. Through this method, neighbouring SNPs within an amplicon can be combined to generate multi-allelic short-read haplotypes (haplotags) that capture recombination history between the constituent SNPs, and reflect the allelic diversity of a given locus in a different way than single bi-allelic SNPs. We found a total of 37 unique QTL across both marker types. A core of 10 QTL were detected with SNPs as well as with haplotags. Haplotags allowed to detect an additional 14 QTL not found based on the SNP set. Conversely, the bi-allelic SNP set also found 13 QTL not detectable using the haplotag set. We conclude that both marker types should routinely be used in parallel to maximize the QTL detection power. We report 19 novel QTL for nine traits: Skin Smoothness, Sprout Dormancy, Total Tuber Number, Tuber Length, Yield, Chipping Colour, After-cooking Blackening, Cooking Type and Eye depth.

Anti-bacterial, anti-biofilm and synergistic effects of phenazine-based ruthenium(II) complexes.

Antimicrobial resistance has become a global threat to human health, which is coupled with the lack of novel drugs. Metallocompounds have emerged as promising diverse scaffolds for the development of new antibiotics. Herein, we prepared some metal compounds mainly focusing on cis-[Ru(bpy)(dppz)(SO3)(NO)](PF6) (PR02, bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine), in which phenazinic and nitric oxide ligands along with sulfite conferred some key properties. This compound exhibited a redox potential for bound NO+/0 of -0.252 V (vs. Ag|AgCl) and a high pH for nitrosyl-nitro conversion of 9.16, making the nitrosyl ligand the major species. These compounds were still able to bind to DNA structures. Interestingly, reduced glutathione (GSH) was unable to promote significant NO/HNO release, an uncommon feature of many similar systems. However, this reducing agent was essential to generate superoxide radicals. Antimicrobial studies were carried out using six bacterial strains, where none or very low activity was observed for Gram-negative bacteria. However, PR02 and PR (cis-[Ru(bpy)(dppz)Cl2]) showed high antibacterial activity in some Gram-positive strains (MBC for S. aureus up to 4.9 µmol L-1), where the activity of PR02 was similar to or at least 4-fold better than that of PR. Besides, PR02 showed capacity to inhibit bacterial biofilm formation, a major health issue leading to bacterial tolerance to antibiotics. Interestingly, we also showed that PR02 can function in synergism with the known antibiotic ampicillin, improving their action up to 4-fold even against resistant strains. Altogether, these results showed that PR02 is a promising antimicrobial nitrosyl ruthenium compound combining features beyond its killing action, which deserves further biological studies.

Lyophilization as an alternative for conservation of equine plasma as a source of immunoglobulin G for neonatal foals.

Providing plasma with immunoglobulins is essential for the health of foals with failure of passive transfer of immunity. The use of lyophilized plasma (LP) offers a simple and affordable option in terms of transportation and storage. This study aimed to measure the concentrations of immunoglobulin G (IgG), total protein (TP), and total solids (TS) in fresh equine plasma before and after lyophilization. Plasma was collected from six healthy male horses. The samples underwent freeze-drying and were reconstituted in deionized water to their original volume. The concentrations of IgG in both fresh and reconstituted LP were determined by simple radial immunodiffusion and TS and TP concentrations measured using refractometry. Results indicated that the IgG concentration in fresh plasma (8.9 ± 3.2 g/L) was not different from LP (7.1 ± 2.2 g/L; P > 0.05). The TP concentration in fresh plasma was 6.6 ± 0.5 g/dL, which decreased to 5.7 ± 0.2 g/dL after lyophilization (P < 0.05). The TS of fresh plasma were 7.5 ± 0.8 %, and also lower in LP 6.3 ± 0.5 % (P < 0.05). The findings revealed that the lyophilization process preserves IgG concentration with small losses in TS and TP upon reconstitution. The research supports the potential of lyophilized equine plasma as a promising treatment option, with future efforts focused on optimizing the product, validating its efficacy and stability through clinical trials, and developing practical packaging solutions for use in the equine industry.

Predictors of the efficacy of His bundle pacing in patients with a prolonged PR interval: A stratified analysis of the HOPE-HF randomized controlled trial.

AIMS: The randomized, double-blind, placebo-controlled HOPE-HF trial assessed the benefit of atrio-ventricular (AV) delay optimization delivered using His bundle pacing. It recruited patients with left ventricular ejection fraction ≤40%, PR interval ≥200 ms, and baseline QRS ≤140 ms or right bundle branch block. Overall, there was no significant increase in peak oxygen uptake (VO2max) but there was significant improvement in heart failure specific quality of life. In this pre-specified secondary analysis, we evaluated the impact of baseline PR interval, echocardiographic E-A fusion, and the magnitude of acute high-precision haemodynamic response to pacing, on outcomes. METHODS AND RESULTS: All 167 randomized participants underwent measurement of PR interval, acute haemodynamic response at optimized AV delay, and assessment of presence of E-A fusion. We tested the impact of these baseline parameters using a Bayesian ordinal model on VO2max, quality of life and activity measures. There was strong evidence of a beneficial interaction between the baseline acute haemodynamic response and the blinded benefit of pacing for VO2 (Pr 99.9%), Minnesota Living With Heart Failure (MLWHF) (Pr 99.8%), MLWHF physical limitation score (Pr 98.9%), EQ-5D visual analogue scale (Pr 99.6%), and exercise time (Pr 99.4%). The baseline PR interval and the presence of baseline E-A fusion did not have this reliable ability to predict the clinical benefit of pacing over placebo across multiple endpoints. CONCLUSIONS: In the HOPE-HF trial, the acute haemodynamic response to pacing reliably identified patients who obtained clinical benefit. Patients with a long PR interval (≥200 ms) and left ventricular impairment who obtained acute haemodynamic improvement with AV-optimized His bundle pacing were likely to obtain clinical benefit, consistent across multiple endpoints. Importantly, this gradation can be reliably tested for before randomization, but does require high-precision AV-optimized haemodynamic assessment to be performed.