Similar Profiles Research Articles

Effect of Layer Addition on Residual Stresses of Wire Arc Additive Manufactured Stainless Steel Specimens

Abstract Residual stresses have been characterized in four Wire Arc Additive Manufacturing specimens with neutron diffraction technique. First, two methods are investigated for obtaining the reference diffracted angle θ0 that is required for the computation of microstrains and, thus, the stresses; θ0 was obtained with two approaches. The first one required a strain-free specimen in order to get directly the reference diffracted angles θ0 in the three principal directions. The second one is based on the plane stress assumption to get θ0 indirectly by imposing that the normal stress was equal to zero. Both methods led to similar residual stress profiles for the one-layer specimen which validated this approach for all specimens without a strain-free specimen available. The second part of this work focused on the modification of the residual stresses in the specimen following the addition of a new deposit. The neutron diffraction measurements showed that the longitudinal stress was tensile in the heat-affected and fusion zones with a maximum value located at the parent material–layers interface where the thermal loadings were applied. A decrease of this maximum value from 257 MPa to 199 MPa appeared after deposition of a new layer which is due to some stress relaxation effect. Inside the parent material, a large zone presents compressive longitudinal stress up to −170 MPa. The bottom part of the parent material is under tensile stress likely due to its upward bending following the thermal contraction of the deposited layers during cooling to ambient temperature.

An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells.

Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.

Comparison of polycrystalline and epitaxial Cu(In, Ga)Se2 solar cells with conversion efficiencies of more than 21%

Polycrystalline Cu(In,Ga)Se2 (CIGS) solar cells are widely studied for their application in thin-film photovoltaics, but analysis of their crystalline properties is difficult owing to the presence of grain boundaries and defects. Epitaxial CIGS (epi-CIGS) solar cells can potentially address the issues of polycrystalline CIGS (poly-CIGS) solar cells, but their conversion efficiency has not been widely studied. We fabricated epi-CIGS layers using techniques developed for high-efficiency ploy-CIGS solar cells such as Ga grading, Na doping, and heat-light soaking. Here, scanning transmission electron microscopy and secondary ion mass spectrometry were used to compare the structural characteristics of poly- and epi-CIGS solar cells with conversion efficiencies of more than 21%. Both types of solar cells had similar Ga gradient profiles, and abrupt interfaces were observed between the CIGS and Mo, CIGS and GaAs, and CdS and CIGS layers. The poly-CIGS layer had a higher Na concentration than the epi-CIGS layer because the grain boundaries of the former included high concentrations of Na ions. Meanwhile, the Na ions in the epi-CIGS layer promoted the interdiffusion of In and Ga. For both types of solar cells, heat-light soaking increased the carrier concentration by more than 1 × 1017 cm−3. These observations suggest that grain boundaries are not the main factor limiting the conversion efficiency of poly-CIGS solar cells.

A screening study of elemental composition in legume (Fabaceae sp.) cultivar from Serbia: Nutrient accumulation and risk assessment

The study is the first analytical approach to evaluate thirteen elements’ profiles of 4 different species (Phaseolus spp., Vicia spp., Pisum spp. and Lathyrus spp.) comprising 38 varieties of legumes cultivated in Serbia. The inductively coupled plasma with an optical emission spectrometer (ICP-OES) was used to determine the levels of macro-, micro- and trace elemental contents, namely, P, K, Ca, Mg, Fe, Cu, Zn, Mn, Cd, Pb, Ni, Cr and As, after microwave-assisted digestion. MANOVA was utilized to reveal significant differences in elemental composition within and between groups, while PCA to reveal the underlying patterns. Among the macroelements, the most abundant was K (8980.7–14177.4 mg kg−1), followed by P, Mg and Ca, being the highest in Phaseolus spp. The data revealed that the studied legumes generally contained a high amount of Zn and Fe, with Lathyrus spp. being the richest in Zn. The mean concentration of trace elements in the analyzed legume samples was in the following order: Ni (24.2–57 mg kg−1) > Cr (0.8–4.1 mg kg−1) > Pb (0.07–1.2 mg kg−1) > Cd (0–0.07 mg kg−1). The determined Pb and Cd contents in all cultivars exceeded the set maximum limits by European and Serbian legislation, having a potential for human health risk. Pattern recognition techniques applied to the data did not distinguish among the species, revealing a similar elemental profile. In conclusion, this study highlights legumes as an extremely valuable source of macro- and microelements, but also the importance of monitoring the level of heavy metals in this commonly consumed foodstuff.

Radiolabeling Diaminosarcophagine with Cyclotron-Produced Cobalt-55 and [55Co]Co-NT-Sarcage as a Proof of Concept in a Murine Xenograft Model.

Cobalt-sarcophagine complexes exhibit high kinetic inertness under various stringent conditions, but there is limited literature on radiolabeling and in vivo positron emission tomography (PET) imaging using no carrier added 55Co. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with 55Co, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [55Co]CoCl2 to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [55Co]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice. The [55Co]Co-DSar complex can be formed at 37 °C with purity and stability suitable for preclinical in vivo radiopharmaceutical applications, and [55Co]Co-NT-Sarcage demonstrated prominent tumor uptake with a low background signal. In a direct comparison with [64Cu]Cu-NT-Sarcage, [55Co]Co-NT-Sarcage achieved a higher tumor-to-liver ratio but with overall similar biodistribution profile. These results demonstrate that Sar would be a promising chelator for constructing Co-based radiopharmaceuticals including 55Co for PET and 58mCo for therapeutic applications.

Targeting Lewy body dementia with neflamapimod-rasagiline hybrids.

Lewy body dementia (LBD) represents the second most common neurodegenerative dementia but is a quite underexplored therapeutic area. Nepflamapimod (1) is a brain-penetrant selective inhibitor of the alpha isoform of the mitogen-activated serine/threonine protein kinase (MAPK) p38α, recently repurposed for LBD due to its remarkable antineuroinflammatory properties. Neuroprotective propargylamines are another class of molecules with a therapeutical potential against LBD. Herein, we sought to combine the antineuroinflammatory core of 1 and the neuroprotective propargylamine moiety into a single molecule. Particularly, we inserted a propargylamine moiety in position 4 of the 2,6-dichlorophenyl ring of 1, generating neflamapimod-propargylamine hybrids 3 and 4. These hybrids were evaluated using several cell models, aiming to recapitulate the complexity of LBD pathology through different molecular mechanisms. The N-methyl-N-propargyl derivative 4 showed a nanomolar p38α-MAPK inhibitory activity (IC50 = 98.7 nM), which is only 2.6-fold lower compared to that of the parent compound 1, while displaying no hepato- and neurotoxicity up to 25 μM concentration. It also retained a similar immunomodulatory profile against the N9 microglial cell line. Gratifyingly, at 5 μM concentration, 4 demonstrated a neuroprotective effect against dexamethasone-induced reactive oxygen species production in neuronal cells that was higher than that of 1.

Different Immunologic Profiles Are Associated With Distinct Clinical Phenotypes in Longitudinally Observed Patients With Systemic Lupus Erythematosus.

The aim of this study was to determine the immunologic profile associated with disease flares in patients with systemic lupus erythematosus (SLE) and to investigate the clinical significance of any differences observed between patients during and following a flare. Multiparameter flow cytometry was used to examine 47 immune populations within the peripheral blood of 16 healthy controls, 25 patients with clinically quiescent SLE, and 46 patients with SLE experiencing a flare at baseline and at 6- and 12-month follow-up visits. Unsupervised clustering was used to identify patients with similar immune profiles and to track changes over time. Parametric or nonparametric statistics were used when appropriate to assess the association of cellular phenotypes with clinical and laboratory parameters. Five clusters of patients were identified that variably contained patients with active and quiescent SLE, and that had distinct clinical phenotypes. Patients characterized by increased T peripheral helper, activated B, and age-associated B cells were the most likely to be flaring at baseline, as well as the most likely to remain active or flare over the subsequent year if they acquired or retained this phenotype at follow-up. In contrast, patients who had increased T helper (Th) cells in the absence of B cell changes, or who had increased Th1 cells and innate immune populations, mostly developed quiescent SLE on follow-up. A significant proportion of patients with SLE had depletion of many immune populations at flare and only showed increases in these populations post-flare. Cellular phenotyping of patients with SLE reveals several distinct immunologic profiles that may help to stratify patients with regard to prognosis and treatment.

Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies

Ex vivo cellular system that accurately replicates sickle cell disease and β-thalassemia characteristics is a highly sought-after goal in the field of erythroid biology. In this study, we present the generation of erythroid progenitor lines with sickle cell disease and β-thalassemia mutation using CRISPR/Cas9. The disease cellular models exhibit similar differentiation profiles, globin expression and proteome dynamics as patient-derived hematopoietic stem/progenitor cells. Additionally, these cellular models recapitulate pathological conditions associated with both the diseases. Hydroxyurea and pomalidomide treatment enhanced fetal hemoglobin levels. Notably, we introduce a therapeutic strategy for the above diseases by recapitulating the HPFH3 genotype, which reactivates fetal hemoglobin levels and rescues the disease phenotypes, thus making these lines a valuable platform for studying and developing new therapeutic strategies. Altogether, we demonstrate our disease cellular systems are physiologically relevant and could prove to be indispensable tools for disease modeling, drug screenings and cell and gene therapy-based applications.

Impact of crystal polymorphism of rifaximin on dissolution behavior

IntroductionRifaximin is an intestinal antiseptic which has five (pseudo) polymorphs α, β, γ, δ and ε. These last (pseudo)polymorphs have different physicochemical properties. The objective of the study is to assess the impact of rifaximin polymorphism on its dissolution rate which could affect its bioavailability. Material and methodsThe analytical validation of dissolution assay method by UV–Visible spectrophotometry was carried out according to ICH Q2. The physicochemical characterization (solubility test, FTIR, DSC, XRD) was carried out on four active pharmaceutical ingredient (MP1, MP2, MP3, MP4). MP1 and MP2 were used by the manufacturer of generic brand 1 (G1) and MP3 and MP4 were used by the manufacturer of generic brand 2 (G2). The comparative in-vitro dissolution study was carried out on the leader brand (P), G1 and G2. ResultsThe four MPs were analyzed by XRD. The results of analysis showed that MP1 and MP4 were a mixture of α form and amorphous form. MP2 had an amorphous form and MP3 had a crystalline form β. The spectra of FTIR showed that the four MP had characteristics bands of rifaximin in the domain 4000-400 cm−1. The differences between the spectra of the four MPs were observed among the amorphous form (MP2), around the region 1800 to 1820 cm−1 which is attributed to the vibration of the CO group. An additional difference observed among the amorphous form (MP2) is around the region 1400 cm−1 which is attributed to the banding OH. The thermograms of MP1, MP2 and MP4 showed endothermic peaks which are probably attributed to the departure of water which indicate that MP1, MP2 and MP4 are pseudopolymoph (hydrate). For the four MPs, probably the melting points are interrupted by the phenomenon of phase transformations (Crystallization) which are reflected by exothermic peaks around 200°C–250 °C.Our results showed that the crystalline polymorphism of rifaximin influences its solubility. According to the results of the solubility test, the β crystal form of rifaximin (MP3) had the lowest solubility (3.47 μg/ml). MP2 had the highest solubility (8.35 μg/ml) and MP1 and MP4 had intermediate solubilities (5.47 μg/ml and 6.74 μg/ml). Comparative in vitro dissolution results showed that the dissolution profile of P was not similar to that of G1 and G2 (% dissolution (P)30min = 60%; % dissolution (G1) 30 min = 100% and % dissolution (G2) 30 min = 115%; f1(P versus G1) = 44; f1(P versus G2) = 61) in M1, while G1 and G2 had comparatively similar dissolution profiles (% dissolution (G1) 30 min = 100%; % dissolution (G1) 30 min = 110%; f1 (G1 versus G2) = 14) in M1. ConclusionThis study highlighted the impact of rifaximin polymorphism on its physico-chemical properties (crystal structure, thermal behavior, solubility) and on its dissolution behavior which could affect the rifaximin bioavailability.

Quantifying Imaging Agent Binding and Dissociation in 3-D Cancer Spheroid Tissue Culture Using Paired-Agent Principles.

Binding kinetics play an important role in cancer diagnosis and therapeutics. However, current methods of quantifying binding kinetics fail to consider the three-dimensional environment that drugs and imaging agents experience in biological tissue. In response, a methodology to assay agent binding and dissociation in 3-D tissue culture was developed using paired-agent molecular imaging principles. To test the methodology, the uptakes of ABY-029 (an IRDye 800CW-labeled epidermal growth factor receptor (EGFR)-targeted antibody mimetic) and IRDye-700DX carboxylate in 3-D spheroids were measured in four different human cancer cell lines throughout staining and rinsing. A compartment model (optimized for the application) was then fit to the kinetic curves of both imaging agents to estimate binding and dissociation rate constants of the EGFR-targeted ABY-029 agent. A statistically significant correlation was observed between apparent association rate constant (k3) and the receptor concentration experimentally and in simulations (r = 0.99, p < 0.05). A statistically significant difference was found between effective k3 (apparent rate constant of ABY-029 binding to EGFR) values for cell lines with varying levels of EGFR expression (p < 0.05), with no significant difference found between cell lines and controls for other fit parameters. Additionally, a similar binding affinity profile compared to a gold standard method was determined by this model. This low-cost methodology to quantify imaging agent or drug binding affinity in clinically relevant 3-D tumor spheroid models can be used to guide timing of imaging in molecular guided surgery and could have implications in drug development.

Fatty Acid Methyl Ester Profiling of Californian Xylella fastidiosa Strains

Xylella fastidiosa ssp. fastidiosa ( Xff) is the causal agent of Pierce's disease of grapevine, a management-intensive and potentially deadly disease. However, different stains and other subspecies, such as Xylella fastidiosa ssp. multiplex ( Xfm), exist in the same regions and vary in capacity to cause disease. All strains differ in the fatty acids that comprise cell membranes, as these allow adaptations to specific host microenvironments. Therefore, studies were initiated to observe the fatty acid profiles of different Californian Xf isolates via fatty acid methyl ester (FAME) analysis. Observations revealed that the four Xff strains had similar FAME profiles that were distinct from those of the three Xfm strains, even in isolates that originated from the same host plant species. These data show consistent differences between Xff and Xfm strains and demonstrate the potential that FAME profiling has for Xylella subspecies identification of novel isolates. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.

In vivo assessment of marine vs bovine origin collagen-based composite scaffolds promoting bone regeneration in a New Zealand rabbit model

The ability of human tissues to self-repair is limited, which motivates the scientific community to explore new and better therapeutic approaches to tissue regeneration. The present manuscript provides a comparative study between a marine-based composite biomaterial, and another composed of well-established counterparts for bone tissue regeneration. Blue shark skin collagen was combined with bioapatite obtained from blue shark's teeth (mColl:BAp), while bovine collagen was combined with synthetic hydroxyapatite (bColl:Ap) to produce 3D composite scaffolds by freeze-drying. Collagens showed similar profiles, while apatite particles differed in their composition, being the marine bioapatite a fluoride-enriched ceramic.The marine-sourced biomaterials presented higher porosities, improved mechanical properties, and slower degradation rates when compared to synthetic apatite-reinforced bovine collagen. The in vivo performance regarding bone tissue regeneration was evaluated in defects created in femoral condyles in New Zealand rabbits twelve weeks post-surgery. Micro-CT results showed that mColl:BAp implanted condyles had a slower degradation and an higher tissue formation (17.9 ± 6.9 %) when compared with bColl:Ap implanted ones (12.9 ± 7.6 %). The histomorphometry analysis provided supporting evidence, confirming the observed trend by quantifying 13.1 ± 7.9 % of new tissue formation for mColl:BAp composites and 10.4 ± 3.2 % for bColl:Ap composites, suggesting the potential use of marine biomaterials for bone regeneration.

Benchmarking glycoform-resolved affinity separation - mass spectrometry assays for studying FcγRIIIa binding.

The antibody- FcγRIIIa interaction triggers key immunological responses such as antibody dependent cellular cytotoxicity (ADCC), making it highly important for therapeutic mAbs. Due to the direct glycan-glycan interaction with FcγRIIIa receptor, differences in antibody glycosylation can drastically influence the binding affinity. Understanding the differential binding of mAb glycoforms is a very important, yet challenging task due to the co-existence of multiple glycoforms in a sample. Affinity liquid chromatography (AC) and affinity capillary electrophoresis (ACE) hyphenated with mass spectrometry (MS) can provide glycoform-resolved affinity profiles of proteins based on their differences in either dissociation (AC) or equilibrium (ACE) constants. To cross-validate the affinity ranking provided by these complementary novel approaches, both techniques were benchmarked using the same FcγRIIIa constructs. Both approaches were able to assess the mAb - FcγRIIIa interaction in a glycoform selective manner and showed a clear increase in binding for fully versus hemi-fucosylated mAbs. Also, other features, such as increasing affinity with elevated galactosylation or the binding affinity for high mannose glycoforms were consistent. We further applied these approaches to assess the binding towards the F158 allotype of FcγRIIIa, which was not reported before. The FcγRIIIa F158 allotype showed a very similar profile compared to the V158 receptor with the strongest increase in binding due to afucosylation and only a slight increase in binding with additional galactosylation. Both techniques showed a decrease of the binding affinity for high mannose glycoforms for FcγRIIIa F158 compared to the V158 variant. Overall, both approaches provided very comparable results in line with orthogonal methods proving the capabilities of separation-based affinity approaches to study FcγR binding of antibody glycoforms.

Visible Consumption, Income Inequality and Social Comparisons. Evidence from Four Latin American Countries

Increased conspicuous consumption motivated by status-seeking behavior can undermine the gains in well-being derived from economic growth. Using expenditure surveys from Argentina, Brazil, Mexico and Uruguay, we assess visible consumption motivated by status seeking behaviour, analyzing different hypotheses about the role of externalities driven by social comparisons and income inequality. Specifically, we provide evidence for the relevance of different reference groups, assessing comparisons with richer (Veblen effects), poorer and similar profile groups (Duesenberry effects). We show that individuals are affected by multiple reference groups. Regarding between-group inequality, we find that individuals mainly seek to differentiate themselves from poorer groups, rather than imitating richer ones. In all cases, average reference group income of similar profile individuals is negatively related to visible consumption. Meanwhile, within-reference group responses are relevant in Argentina, Brazil and Mexico: increased visible goods consumption is associated with larger relative income gaps. In Argentina and Brazil, the sensitivity of visible goods expenditures to income is higher among households located above the reference threshold, which is consistent, again, with more affluent households trying to signal status by differentiating themselves from the most deprived group members. Meanwhile, in the case of Mexico, there is a symmetric response.

High pesticide exposure and risk to bees in pollinator plantings adjacent to conventionally managed blueberry fields

Wildflower plantings adjacent to agricultural fields provide diverse floral resources and nesting sites for wild bees. However, their proximity to pest control activities in the crop may result in pesticide exposure if pesticides drift into pollinator plantings. To quantify pesticide residues in pollinator plantings, we sampled flowers and soil from pollinator plantings and compared them to samples from unenhanced field margins and crop row middles. At conventionally managed farms, flowers from pollinator plantings had similar exposure profiles to those from unenhanced field margins or crop row middles, with multiple pesticides and high and similar risk quotient (RQ) values (with pollinator planting RQ: 3.9; without pollinator planting RQ: 4.0). Whereas samples from unsprayed sites had significantly lower risk (RQ: 0.005). Soil samples had overall low risk to bees. Additionally, we placed bumble bee colonies (Bombus impatiens) in field margins of crop fields with and without pollinator plantings and measured residues in bee-collected pollen. Pesticide exposure was similar in pollen from sites with or without pollinator plantings, and risk was generally high (with pollinator planting RQ: 0.5; without pollinator planting RQ: 1.1) and not significant between the two field types. Risk was lower at sites where there was no pesticide activity (RQ: 0.3), but again there was no significant difference between management types. The insecticide phosmet, which is used on blueberry farms for control of Drosophila suzukii, accounted for the majority of elevated risk. Additionally, analysis of pollen collected by bumble bees found no significant difference in floral species richness between sites with or without pollinator plantings. Our results suggest that pollinator plantings do not reduce pesticide risk and do not increase pollen diversity collected by B. impatiens, further highlighting the need to reduce exposure through enhanced IPM adoption, drift mitigation, and removal of attractive flowering weeds prior to insecticide applications.

Assessment of the Nutritional Potential and Resistance to Oxidation of Sea Buckthorn and Rosehip Oils

Cold-pressed oils from non-typical materials, such as wild rose and sea buckthorn, should meet certain requirements to be approved for consumption. The aim of this study was to evaluate the nutritional potential and selected quality parameters with particular emphasis on oxidative stability of two commercially available cold-pressed oils: rose hip oil and sea buckthorn oil. The fatty acid composition, including nutritional indexes (polyunsaturated fatty acid/saturated fatty acid ratio PUFA/SFA; atherogenicity index IA is as follows: hypocholesterolemic/hypercholesterolemic index HH; health-promoting index HPI), positional distribution of fatty acids, melting profile and oxidative stability were analyzed. The tested oils were characterized by a high content of unsaturated fatty acids, which were mainly represented by oleic and linoleic acids. In the case of one of the analyzed rosehip oil oils (R1), α-linolenic acid was also found at the level of 26%, which contributed to obtaining the recommended ratio of omega-6 to omega-3 fatty acids. The lowest value of IA and the highest values of HH and HPI were also recorded for R1 rosehip oil. This oil was also characterized by the highest resistance to oxidation, as indicated by induction times measured at various temperatures. The distribution of fatty acids in triacylglycerols molecules in the analyzed oils was typical for vegetable oils. In the case of tested oils, similar melting profiles with endothermic peaks recorded at negative temperatures, which resulted from the presence of triacylglycerol fractions with a high proportion of mono- and polyunsaturated fatty acids, were observed.

In-hospital safety outcomes of left atrial appendage occlusion in octogenarians and nonagenarians.

Data on safety outcomes of left atrial appendage occlusion (LAAO) in elderly patients are limited. This study aimed to compare the outcomes of LAAO between octogenarians (age 80-89) and nonagenarians (age ≥90) vs. younger patients (age ≤79). We conducted a retrospective cohort study using the National Inpatient Sample database to identify patients hospitalized for LAAO from 2016 to 2020 and to compare in-hospital safety outcomes in octogenarians and nonagenarians vs. younger patients. The primary outcome was a composite of in-hospital all-cause mortality or stroke. Secondary outcomes included procedural complications, length of stay (LOS), and total costs. Outcomes were determined using logistic regression models. Among 84 140 patients hospitalized for LAAO, 32.9% were octogenarians, 2.8% were nonagenarians, and 64.3% were ≤79 years of age. Over the study period, the volume of LAAO increased in all age groups (all Ptrend < 0.01). After adjustment for clinical and demographic factors, octogenarians and nonagenarians had similar odds of in-hospital all-cause mortality or stroke [adjusted odds ratio (aOR) 1.41, 95% confidence interval (CI) 0.93-2.13 for octogenarians; aOR 1.69, 95% CI 0.67-3.92 for nonagenarians], cardiac tamponade, acute kidney injury, major bleeding, and blood transfusion, in addition to similar LOS and total costs compared with younger patients (all P > 0.05). However, octogenarians and nonagenarians had higher odds of vascular complications compared with younger patients (aOR 1.47, 95% CI 1.08-1.99 for octogenarians; aOR 1.60, 95% CI 1.18-2.97 for nonagenarians). Octogenarians and nonagenarians undergoing LAAO have a similar safety profile compared with clinically similar younger patients except for higher odds of vascular complications.

Low Contrast Challenge and Limitations of Thermal Drones in Maritime Search and Rescue—Pilot Study

This paper analyses the efficiency of thermal infrared (TIR) systems during night search operations under specific weather conditions, with a focus on determining the maximum operating altitude of the drone. The drone used in the research (DJI Matrice 210 V2) is equipped with a thermal camera, in a scenario involving maritime search and rescue (SAR) operation, i.e., person detection at sea with or without a survival suit. By capturing images from different altitudes and measuring key atmospheric and maritime parameters, essential data are obtained for defining optimal DRI parameters (detection, recognition, and identification) within the existing on-site meteorological conditions. This research contributes to more accurate life-saving procedures, underlining the importance of uncrewed aerial vehicle (UAV) technology for maritime SAR. It is expected that the presented model will improve operational readiness for SAR operations in areas with similar climatic profiles. The research results indicate the need to conduct similar research in different climatic conditions to improve the application of the TIR system in maritime SAR operations.

Trace polymer coated clarithromycin spherulites: Formation mechanism, improvement in pharmaceutical properties and development of high-drug-loading direct compression tablets

Clarithromycin (CLA) is a high dose antibiotic drug exhibiting poor flowability and tabletability, making the tablet development challenging. This study aims to develop spherulitic CLA by introducing trace amount of polymer in crystallization solution. Its formation mechanism, physicochemical properties and potential for the direct compression (DC) tablets development were also investigated. Morphological analyses and the in situ observation on crystallization process revealed that the CLA spherulites are formed by fractal branching growth from both sides of the threadlike precursor fibers. 1H NMR analysis and nucleation time monitoring indicated that the existence of hydroxypropyl cellulose in solution slowed down the crystal nucleation and growth rate by forming hydrogen bonding interactions with CLA molecules, making the system maintain high supersaturation, providing high driving forces for CLA spherulitic growth. In comparison to commercial CLA, the CLA spherulites exhibit profoundly improved flowability, tabletability and dissolution behaviors. XPS, contact angle and Raman mapping analysis confirmed the presence of a thin HPC layer on the surfaces and interior of CLA spherulitic particles, resulting in increasing powder plasticity, interparticulate bonding strength and powder wettability, thus better tabletability and dissolution performances. The improved flowability and tabletability of CLA spherulites also enabled the successful development of DC tablet formulation with a high CLA loading (82.8 wt%) and similar dissolution profiles to reference listed drug. This study provides a novel solid form of CLA with superior manufacturability for further development.

A new and promiscuous α/β hydrolase from Acinetobacter tandoii DSM 14970 T inactivates the mycotoxin ochratoxin A

The presence of ochratoxin A (OTA) in food and feed represents a serious concern since it raises severe health implications. Bacterial strains of the Acinetobacter genus hydrolyse the amide bond of OTA yielding non-toxic OTα and L-β-phenylalanine; in particular, the carboxypeptidase PJ15_1540 from Acinetobacter sp. neg1 has been identified as an OTA-degrading enzyme. Here, we describe the ability to transform OTA of cell-free protein extracts from Acinetobacter tandoii DSM 14970 T, a strain isolated from sludge plants, and also report on the finding of a new and promiscuous α/β hydrolase (ABH), with close homologs highly distributed within the Acinetobacter genus. ABH from A. tandoii (AtABH) exhibited amidase activity against OTA and OTB mycotoxins, as well as against several carboxypeptidase substrates. The predicted structure of AtABH reveals an α/β hydrolase core composed of a parallel, six-stranded β-sheet, with a large cap domain similar to the marine esterase EprEst. Further biochemical analyses of AtABH reveal that it is an efficient esterase with a similar specificity profile as EprEst. Molecular docking studies rendered a consistent OTA-binding mode. We proposed a potential procedure for preparing new OTA-degrading enzymes starting from promiscuous α/β hydrolases based on our results.Key points• AtABH is a promiscuous αβ hydrolase with both esterase and amidohydrolase activities• AtABH hydrolyses the amide bond of ochratoxin A rendering nontoxic OTα• Promiscuous αβ hydrolases are a possible source of new OTA-degrading enzymes