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Abstract An optimized sol–gel protocol was carried out to produce an yttrium aluminum garnet (YAG) xerogel from aluminum alkoxide and an yttrium salt on a semi-pilot scale. This xerogel was successfully used without prior pyrolysis as a solid load with the aid of additives in the preparation of pastes. Thermal treatment of the green bodies, obtained by robocasting of the paste, led to cohesive single-phase YAG ceramics. Manufacturing ceramic pieces by additive methods will allow shaping complex forms, while the single step conversion/consolidation would simplify the technological process, reducing global energy costs. Since YAG possesses high strength and good creep behavior at high temperatures, these refractory pieces could replace the metal alloys used in turbine blades for deep space exploration. Structural, thermal and chemical characterizations were performed on xerogel powders, pastes, and YAG ceramics.

The volume of distribution at steady state (Vss) in neonates is still often estimated through isometric scaling from adult values, disregarding developmental changes beyond body weight. This study aimed to compare the accuracy of two physiologically based pharmacokinetic (PBPK) Vss prediction methods in neonates (Poulin & Theil with Berezhkovskiy correction (P&T+) and Rodgers & Rowland (R&R)) with isometrical scaling. PBPK models were developed for 24 drugs using in-vitro and in-silico data. Simulations were done in Simcyp (V22) using predefined populations. Clinical data from 86 studies in neonates (including preterms) were used for comparison, and accuracy was assessed using (absolute) average fold errors ((A)AFEs). Isometric scaling resulted in underestimated Vss values in neonates (AFE: 0.61), and both PBPK methods reduced the magnitude of underprediction (AFE: 0.82–0.83). The P&T+ method demonstrated superior overall accuracy compared to isometric scaling (AAFE of 1.68 and 1.77, respectively), while the R&R method exhibited lower overall accuracy (AAFE: 2.03). Drug characteristics (LogP and ionization type) and inclusion of preterm neonates did not significantly impact the magnitude of error associated with isometric scaling or PBPK modeling. These results highlight both the limitations and the applicability of PBPK methods for the prediction of Vss in the absence of clinical data.

Numerous studies have shown that alterations in physiological reactivity (PR) after traumatic brain injury (TBI) are possibly associated with emotional deficits. We conducted a systematic review of these studies that evaluated PR in adults with moderate-to-severe TBI, either at rest or in response to emotional, stressful, or social stimuli. We focused on the most common measures of physiological response, including heart rate (HR), heart rate variability (HRV), respiratory sinus arrhythmia (RSA), electrodermal activity (EDA), salivary cortisol, facial electromyography (EMG), and blink reflex.MethodsA systematic literature search was conducted across six databases (PsycINFO, Psycarticles, SciencDirect, Cochrane Library, PubMed, and Scopus). The search returned 286 articles and 18 studies met the inclusion criteria.ResultsDiscrepancies were observed according to the type of physiological measure. Reduced physiological responses in patients with TBI have been reported in most EDA studies, which were also overrepresented in the review. In terms of facial EMG, patients with TBI appear to exhibit reduced activity of the corrugator muscle and diminished blink reflex, while in most studies, zygomaticus contraction did not show significant differences between TBI and controls. Interestingly, most studies measuring cardiac activity did not find significant differences between TBI and controls. Finally, one study measured salivary cortisol levels and reported no difference between patients with TBI and controls.ConclusionAlthough disturbed EDA responses were frequently reported in patients with TBI, other measures did not consistently indicate an impairment in PR. These discrepancies could be due to the lesion pattern resulting from TBI, which could affect the PR to aversive stimuli. In addition, methodological differences concerning the measurements and their standardization as well as the characteristics of the patients may also be involved in these discrepancies. We propose methodological recommendations for the use of multiple and simultaneous PR measurements and standardization. Future research should converge toward a common methodology in terms of physiological data analysis to improve inter-study comparisons.

The origin of the three great epidemics of the Roman period has often been sought in Asia. We propose a review of our knowledge, taking into account the new information provided by archaeology. The commercial circulation between Rome and Asia is better known, in particular for the Indian Ocean. The phylogenetic analysis of microbes made possible by ancient DNA is also beginning to change our knowledge. However, it remains difficult to link the Antonine and Cyprian epidemics with Asia. Justinian's plague, on the other hand, did originate in Central Asia, and then probably took the Indian Ocean trade route.

Objective To investigate risk factors and subphenotypes associated with long term symptoms and outcomes after hospital admission for covid-19.Design Prospective, multicentre observational study.Setting 93 hospitals in France.Participants Data from 2187 adults admitted to hospital with covid-19 in France between 1 February 2020 and 30 June 2021.Main outcome measures Primary endpoint was the total number of persistent symptoms at six months after hospital admission that were not present before admission. Outcomes examined at six months were persistent symptoms, Hospital Anxiety and Depression Scale, six minute walk test distances, 36-Item Short Form Health Survey scores, and ability to resume previous professional activities and self-care. Secondary endpoints included vital status at six months, and results of standardised quality-of-life scores. Additionally, an unsupervised consensus clustering algorithm was used to identify subphenotypes based on the severity of hospital course received by patients.Results 1109 (50.7%) of 2187 participants had at least one persistent symptom. Factors associated with an increased number of persistent symptoms were in-hospital supplemental oxygen (odds ratio 1.12, 95% confidence interval 1 to 1.24), no intensive care unit admission (1.15, 1.01 to 1.32), female sex (1.33, 1.22 to 1.45), gastrointestinal haemorrhage (1.51, 1.02 to 2.23), a thromboembolic event (1.66, 1.17 to 2.34), and congestive heart failure (1.76, 1.27 to 2.43). Three subphenotypes were identified: including patients with the least severe hospital course (based on ventilatory support requirements). Although Hospital Anxiety and Depression Scale scores were within normal values for all groups, patients of intermediate severity and more comorbidities had a higher median Hospital Anxiety and Depression Scale score than did the other subphenotypes. Patients in the subphenotype with most severe hospital course had worse short form-36 scores and were less able to resume their professional activity or care for themselves as before compared with other subphenotypes.Conclusions Persistent symptoms after hospital admission were frequent, regardless of acute covid-19 severity. However, patients in more severe subphenotypes had a significantly worse functional status and were less likely to resume their professional activity or able to take care of themselves as before.Trial registration NCT04262921.

Inkjet printing (IJP) is a prospective additive manufacturing technology that enables the rapid and precise deposition of thin films or patterns. It offers numerous advantages over other thin-film manufacturing processes, including cost-effectiveness, ease of use, reduced waste material, and scalability. The key advantage of this technique is the ability of the fabrication of complex patterns with very high precision. The IJP gives the possibility of building three-dimensional (3D) structures on the microscale, which is beneficial for modern Li-Ion batteries (LIBs) and All-Solid-State Li-Ion Batteries (ASSLIBs). In contrast to typical laminated composite electrodes manufactured by tape casting and calendaring, 3D electrode design allows the electrolyte to penetrate through the electrode volume, increasing the surface-to-volume ratio and reducing ion diffusion paths. Thus, 3D electrodes/electrolyte structures are one of the most promising strategies for producing next-generation lithium-ion batteries with enhanced electrochemical performance. Although in the literature review, the IJP is frequently reported as a future perspective for the fabrication of 3D electrodes/electrolytes structures for LIBs, only a few works focus on this subject. In this review, we summarize the previous studies devoted to the topic and discuss different bottlenecks and challenges limiting further development.

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Previous studies have shown that the incorporation of sulfonated metallophthalocyanines into sensitive sensor materials can improve electron transfer and thus species detection. Herein, we propose a simple and easy alternative to the use of generally expensive sulfonated phthalocyanines by electropolymerizing polypyrrole together with nickel phthalocyanine in the presence of an anionic surfactant. The addition of the surfactant not only helps the incorporation of the water-insoluble pigment into the polypyrrole film, but the obtained structure has increased hydrophobicity, which is a key property for developing efficient gas sensors with low sensitivity to water. The obtained results show the effectiveness of the materials tested for the detection of ammonia in the range of 100 to 400 ppm. It is shown by comparing the microwave sensor responses that the film without nickel phthalocyanine (hydrophilic) produces greater variations than the film with nickel phthalocyanine (hydrophobic). These results are consistent with the expected results since the hydrophobic film is not very sensitive to residual ambient water and therefore does not interfere with the microwave response. However, although this excess response is usually a handicap, as it is a source of drift, in these experiments the microwave response shows great stability in both cases.

Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown. We described blood and BM eosinophil characteristics in SM. A large collection of BM biopsy samples was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence. Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in nonadvanced SM (n = 37 BM biopsy samples) compared with both controls (n = 8, P =.0003) and advanced SM (n = 24, P =.014). In nonadvanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r = 0.38, P =.038), eosinophils count in BM biopsy samples (r = 0.45, P =.007), EPX staining (r = 0.37, P =.035), and eosinophil degranulation (r = 0.39, P =.023). Eosinophil counts in BM biopsy samples also correlated with MC counts (r = 0.47, P =.006) and KIT staining surface (r = 0.49, P =.003). BM MCs expressed IL-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils displayed several increased surface markers compared with controls, suggesting an activated state. Our data suggest possible cross talk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in nonadvanced SM not fully controlled by other therapies. [ABSTRACT FROM AUTHOR]

© 2016 The Author(s). Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

Glioblastomas (GBs) are the most common and malignant brain tumors in adults. A protein encoded by the gene YWHAB, 14-3-3β, is commonly found to be upregulated throughout the initiation and progression of GB. The 14-3-3β has oncogenic roles in several different types of cancer cells through interactions with proteins such as Bad, FBI1, Raf-1, Cdc25b, and others. Previous RNA interference studies have shown that 14-3-3β promotes proliferation, cell cycle progression, and migration and invasion of GB cells. However, despite the many oncogenic functions of 14-3-3β, a CRISPR/Cas9 knockout model of 14-3-3β has not been investigated. This study confirmed previous findings and showed that siRNA inhibition of 14-3-3β results in reduced cellular proliferation in a human glioblastoma cell line, U87MG. We also used a YWHAB Tet-On CRISPR/Cas9 U87MG cell line that, upon doxycycline induction, leads to robust Cas9 expression and subsequent knockout of 14-3-3β. Using this model, we show that loss of 14-3-3β significantly reduces cellular proliferation and spheroid formation of U87MG cells.

Violacein and deoxyviolacein are bis-indole pigments synthesized by a number of microorganisms. The present study describes the biosynthesis of a mixture of violacein and deoxyviolacein using a genetically modified Y. lipolytica strain as a production chassis, the subsequent extraction of the intracellular pigments, and ultimately their purification using column chromatography. The results show that the optimal separation between the pigments occurs using an ethyl acetate/cyclohexane mixture with different ratios, first 65:35 until both pigments were clearly visible and distinguishable, then 40:60 to create a noticeable separation between them and recover the deoxyviolacein, and finally 80:20, which allows the recovery of the violacein. The purified pigments were then analyzed by thin-layer chromatography and nuclear magnetic resonance.

We present an integrated single-photon detection device custom designed for quantum key distribution (QKD) with time-bin encoded single photons. We implemented and demonstrated a prototype photon-to-digital converter (PDC) that integrates an 8 × 8 single-photon avalanche diode (SPAD) array with on-chip digital signal processing built in TSMC 65 nm CMOS. The prototype SPADs are used to validate the QKD functionalities with an array of time-to-digital converters (TDCs) to timestamp and process the photon detection events. The PDC uses window gating to reject noise counts and on-chip processing to sort the photon detections into respective time-bins. The PDC prototype achieved a 22.7 ps RMS timing resolution and demonstrated operation in a time-bin setup with 158 ps time-bins at an optical wavelength of 410 nm. This PDC can therefore be an important building block for a QKD receiver and enables compact and robust time-bin QKD systems with imaging detectors.

Chronic inflammation plays a key role in arterial stiffness pathogenesis. Dietary components can display anti- or pro-inflammatory properties. Nonetheless, the association between the diet's overall inflammatory potential and arterial stiffness is unclear. This study aimed to assess the association between the diet's overall inflammatory potential and arterial stiffness assessed by carotid-femoral pulse wave velocity (cfPWV). This cross-sectional study included 1307 participants from the STANISLAS family cohort study. Dietary data were collected using a validated food frequency questionnaire. The adapted dietary inflammatory index (ADII) score was calculated to assess the inflammatory potential of the participants' diet. The association of ADII score quartile with cfPWV was assessed using IPW-weighted linear mixed models with random family effect. The median (Q1-Q3) ADII score was 0.45 (-1.57, 2.04). Participants exhibiting higher ADII scores demonstrated elevated energy intake, dietary saturated fat, and ultra-processed foods. Conversely, individuals with lower ADII scores exhibited higher vitamins and omega intakes, and a higher diet quality, as assessed by the DASH score. Despite these observations from the descriptive analyses, ADII score quartiles were not significantly associated with cfPWV (β(95% CI) were 0.01 (-0.02,0.04) for Q2, 0.02 (-0.01,0.05) for Q3, and 0.02 (-0.01,0.05) for Q4 compared to Q1). In this cross-sectional study, participants had a relatively modest consumption of pro-inflammatory foods, no substantial associations were observed between the diet inflammatory potential and arterial stiffness. Further longitudinal studies in larger cohorts are needed to better understand the link between inflammatory diet and arterial stiffness. • Chronic inflammation plays a key role in arterial stiffness pathogenesis. • Dietary components can display anti- or pro-inflammatory properties. • Link between diet inflammatory score and arterial stiffness association was studied. • The Adapted Dietary Inflammatory Index (ADII) was fairly neutral with 0.45 as median. • No association were observed between ADII and arterial stiffness. [ABSTRACT FROM AUTHOR]

BackgroundAcute kidney injury (AKI) is one of the most common and significant problems in patients with Coronavirus Disease 2019 (COVID-19). However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional Kidney Disease Improving Global Outcomes (KDIGO) definition can fail to identify patients for whom hospitalisation coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesised that an extended KDIGO (eKDIGO) definition, adapted from the International Society of Nephrology (ISN) 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI (CA-AKI) with similarly poor outcomes as previously reported in this population.Methods and findingsAll individuals recruited using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)-World Health Organization (WHO) Clinical Characterisation Protocol (CCP) and admitted to 1,609 hospitals in 54 countries with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection from February 15, 2020 to February 1, 2021 were included in the study. Data were collected and analysed for the duration of a patient's admission. Incidence, staging, and timing of AKI were evaluated using a traditional and eKDIGO definition, which incorporated a commensurate decrease in sCr. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristics and outcomes-intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital death-were compared for all 3 groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. A total of 75,670 patients were included in the final analysis cohort. Median length of admission was 12 days (interquartile range [IQR] 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7% versus 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% versus 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% versus 23%) invasive ventilation (45% versus 15%), and increased mortality (38% versus 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted odds ratio: 1.78, 95% confidence interval: 1.71 to 1.80, p-value < 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% versus 50% death and 35% versus 70% ICU admission) but significantly higher when compared to patients with no AKI (25% versus 19% death and 35% versus 23% ICU admission) (all p-values ConclusionsAn extended KDIGO definition of AKI resulted in a significantly higher detection rate in this population. These additional cases of AKI occurred early in the hospital admission and were associated with worse outcomes compared to patients without AKI.

With the goal of developing refractory pastes to replace metal alloys used in turbine blades for Deep Space exploration, the French Space Agency, CNES, in collaboration with the Institute of Research for Ceramics, IRCER, has developed a preliminary research where dense alumina ceramics were formulated, printed and tested. This preliminary research will be the prelude to substituting by materials with more interesting creep properties at high temperature, for example, yttrium aluminum garnet, YAG. Since alumina is less expensive than YAG, preliminary tests were performed with alumina. These alumina pastes were 3D-printed by robocasting from very high solid loaded alumina pastes (>75 wt%), in the presence of organic additives, namely glycerol, PVA and ISOBAM 104. Several formulations of pastes were prepared, with the aim to obtain dense ceramic pieces. After, the alumina and the organic additives were mechanically mixed and the pastes were extruded with a commercial 3D printer. The best sample was obtained with a paste presenting an Al2O3 solid load of 79.37 wt% (63.5 vol%). A debinding step was performed afterwards to eliminate their organic content and the consolidation of the shaped pieces was finally achieved by sintering at 1700 °C. A % shrinkage of 8, 6.8 and 13.8 in the X, Y and Z-axes was measured, being one of the lowest values at 1700 °C compared to those in the literature.