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The aim of our study was to assess the impact of the very early introduction of refeeding on the course of acute pancreatitis (AP) in children. Additionally, we evaluated the effect of nutrition on inflammatory markers, including cytokines. This prospective randomised study was conducted in three university hospitals in Poland. Patients, aged 1–18 years with AP, were randomised into two groups: A—refeeding within 24 h of hospital admission (very early), and B—refeeding at least 24 h after admission (early nutrition). The severity of AP was assessed after 48 h. The serum concentrations of four cytokines (tumour necrosis factor α [TNFα], interleukin‐1β [IL‐1β], interleukin‐6 [IL‐6] and interleukin‐8 [IL‐8]) and C‐reactive protein, as well as the activity of amylase, lipase and aminotransferases, were measured during the first 3 days of hospitalisation. A total of 94 children were recruited to participate in the study. The statistical analysis included 75 patients with mild pancreatitis: 42—group A and 33—group B. The two groups did not differ in the length of hospitalisation (p= 0.22), AP symptoms or results of laboratory tests. Analysis of cytokine levels was conducted for 64 children: 38—group A and 26—group B. We did not find a difference in concentrations of the measured cytokines, except for IL‐1β on the third day of hospitalisation (p= 0.01). The time of initiation of oral nutrition within 24 h (very early) or after 24 h (early) from the beginning of hospitalisation had no impact on the length of hospitalisation, concentrations of TNF‐α, IL‐1β, IL‐6 and IL‐8, activity of amylase and lipase or occurrence of symptoms in children with mild AP. •An increasing incidence of acute pancreatitis (AP) in children has been observed in the past three decades.•The results of studies of adults suggest that early oral feeding in AP patients may shorten hospital stays, decrease infectious complications and decrease morbidity and mortality. An increasing incidence of acute pancreatitis (AP) in children has been observed in the past three decades. The results of studies of adults suggest that early oral feeding in AP patients may shorten hospital stays, decrease infectious complications and decrease morbidity and mortality. •Very early nutrition, when compared to early nutrition, had no impact on the length of hospitalisation.•Very early nutrition, when compared to early nutrition, had no impact on the serum concentrations of cytokines (tumour necrosis factor α, interleukin‐1β, interleukin‐6 and interleukin‐8). Very early nutrition, when compared to early nutrition, had no impact on the length of hospitalisation. Very early nutrition, when compared to early nutrition, had no impact on the serum concentrations of cytokines (tumour necrosis factor α, interleukin‐1β, interleukin‐6 and interleukin‐8).

Current developments in laser micromachining involve the transition of the ablation process from gaseous to liquid environments. The properties of the liquid lead to optimized processing results in terms of precision, surface quality, and, notably, reduced thermal defects compared to processing in gas. While these benefits are apparent, the process introduces increased complexity into the interaction between the laser beam and the liquid.

BackgroundVessel perforation during thrombectomy is a severe complication and is hypothesized to be more frequent during medium vessel occlusion (MeVO) thrombectomy. The aim of this study was to compare the incidence and outcome of patients with perforation during MeVO and large vessel occlusion (LVO) thrombectomy and to report on the procedural steps that led to perforation.MethodsIn this multicenter retrospective cohort study, data of consecutive patients with vessel perforation during thrombectomy between January 1, 2015 and September 30, 2022 were collected. The primary outcomes were independent functional outcome (ie, modified Rankin Scale 0–2) and all-cause mortality at 90 days. Binomial test, chi-squared test and t-test for unpaired samples were used for statistical analysis.ResultsDuring 25 769 thrombectomies (5124 MeVO, 20 645 LVO) in 25 stroke centers, perforation occurred in 335 patients (1.3%; mean age 72 years, 62% female). Perforation occurred more often in MeVO thrombectomy (2.4%) than in LVO thrombectomy (1.0%, p<0.001). More MeVO than LVO patients with perforation achieved functional independence at 3 months (25.7% vs 10.9%, p=0.001). All-cause mortality did not differ between groups (overall 51.6%). Navigation beyond the occlusion and retraction of stent retriever/aspiration catheter were the two most common procedural steps that led to perforation.ConclusionsIn our cohort, perforation was approximately twice as frequent in MeVO than in LVO thrombectomy. Efforts to optimize the procedure may focus on navigation beyond the occlusion site and retraction of stent retriever/aspiration catheter. Further research is necessary in order to identify thrombectomy candidates at high risk of intraprocedural perforation and to provide data on the effectiveness of endovascular countermeasures.

BackgroundSpinal cord (SC) lesions have been associated with unfavourable clinical outcomes in multiple sclerosis (MS). However, the relation of whole SC lesion number (SCLN) and volume (SCLV) to the future occurrence and type of confirmed disability accumulation (CDA) remains largely unexplored.MethodsIn this monocentric retrospective study, SC lesions were manually delineated. Inclusion criteria were: age between 18 and 60 years, relapsing-remitting MS, disease duration under 2 years and clinical follow-up of 5 years. The first CDA event after baseline, determined by a sustained increase in the Expanded Disability Status Scale over 6 months, was classified as either progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW). SCLN and SCLV were compared between different (sub)groups to assess their prospective value.Results204 patients were included, 148 of which had at least one SC lesion and 59 experienced CDA. Patients without any SC lesions experienced significantly less CDA (OR 5.8, 95% CI 2.1 to 19.8). SCLN and SCLV were closely correlated (rs=0.91, p<0.001) and were both significantly associated with CDA on follow-up (p<0.001). Subgroup analyses confirmed this association for patients with PIRA on CDA (34 events, p<0.001 for both SC lesion measures) but not for RAW (25 events, p=0.077 and p=0.22).ConclusionPatients without any SC lesions are notably less likely to experience CDA. Both the number and volume of SC lesions on MRI are associated with future accumulation of disability largely independent of relapses.

A quasi-experimental study with ninth graders evaluated a 1.5-hour hate speech teaching unit in an intervention vs. control group (N= 82) before (T1) and after the intervention (T2). Participants reported frequency of witnessing hate speech (T1), hate speech norm and self-efficacy countering hate speech (T1 and T2), and knowledge concerning hate speech (T2). Repeated ANOVAs showed a significant three-way interaction for hate speech norm: Especially among those who witnessed hate speech more often, the program diminished the agreement to hate speech norm. Self-efficacy did not change significantly, but knowledge was slightly higher in the intervention group, particularly among students with a migration background. In sum, the intervention showed effects on norms and knowledge, and longer programs with more interactive elements for coping with hate speech seem recommendable. The current research is a first step and evidence-based practice for prevention of hate speech like the current evaluation study is desperately needed.

Despite the great progress in the colloidal syntheses of plasmonic metal nanoparticles, batch processes still face a general limitation toward achieving large-scale production and reproducibility, due to insufficient control over reagent addition conditions and other reaction parameters, such as mixing rate, temperature, etc. Flow reactors provide the opportunity to counteract the limitations of traditional batch nanomaterials synthesis. We demonstrate the use of a purposely devised millifluidic flow reactor for the seeded growth of monodisperse gold nanoparticles with high process control and batch-to-batch reproducibility. This system offers versatility toward the synthesis of various gold nanoparticle shapes and dimensions, as demonstrated here for nanospheres, nanorods, and nanostars.

Following severe liver injury, when hepatocyte-mediated regeneration is impaired, biliary epithelial cells (BECs) can transdifferentiate into functional hepatocytes. However, the subset of BECs with such facultative tissue stem cell potential, as well as the mechanisms enabling transdifferentiation, remains elusive. Here we identify a transitional liver progenitor cell (TLPC), which originates from BECs and differentiates into hepatocytes during regeneration from severe liver injury. By applying a dual genetic lineage tracing approach, we specifically labeled TLPCs and found that they are bipotent, as they either differentiate into hepatocytes or re-adopt BEC fate. Mechanistically, Notch and Wnt/β-catenin signaling orchestrate BEC-to-TLPC and TLPC-to-hepatocyte conversions, respectively. Together, our study provides functional and mechanistic insights into transdifferentiation-assisted liver regeneration.

The roof plate-specific spondin–leucine-rich repeat-containing G-protein coupled receptor 4/5 (LGR4/5)–zinc and ring finger 3 (ZNRF3)/ring finger protein 43 (RNF43) module is a master regulator of hepatic Wnt/β-catenin signaling and metabolic zonation. However, its impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. The current study investigated whether hepatic epithelial cell-specific loss of the Wnt/β-catenin modulator Lgr4/5 promoted NAFLD. The 3- and 6-month–old mice with hepatic epithelial cell-specific deletion of both receptors Lgr4/5 (Lgr4/5dLKO) were compared with control mice fed with normal diet (ND) or high-fat diet (HFD). Six-month–old HFD-fed Lgr4/5dLKO mice developed hepatic steatosis and fibrosis but the control mice did not. Serum cholesterol–high-density lipoprotein and total cholesterol levels in 3- and 6-month–old HFD-fed Lgr4/5dLKO mice were decreased compared with those in control mice. An ex vivoprimary hepatocyte culture assay and a comprehensive bile acid (BA) characterization in liver, plasma, bile, and feces demonstrated that ND-fed Lgr4/5dLKO mice had impaired BA secretion, predisposing them to develop cholestatic characteristics. Lipidome and RNA-sequencing analyses demonstrated severe alterations in several lipid species and pathways controlling lipid metabolism in the livers of Lgr4/5dLKO mice. In conclusion, loss of hepatic Wnt/β-catenin activity by Lgr4/5 deletion led to loss of BA secretion, cholestatic features, altered lipid homeostasis, and deregulation of lipoprotein pathways. Both BA and intrinsic lipid alterations contributed to the onset of NAFLD.

Shape memory polymer composites (SMPCs) have gained attention for their shape memory effects and wide-ranging applications. Understanding the bending shape recovery characteristics of 3D printed SMPCs is crucial for optimizing their performance. This study focuses on investigating the influence of different fiber orientations of continuous carbon fiber (CCF) in thermally stimulated SMPC. By controlling printing parameters and fiber orientation during the 3D printing process, we fabricate tailor-made rectangular composite test specimens. These specimens are subjected to controlled bending above the glass transition temperature of the polymer, inducing temporary deformation. The subsequent shape recovery process is carefully captured through high-speed video. Precise measurements of the bending curvature over time are obtained using the row-by-row image processing technique and analyzed. The shape recovery rate, shape recovery ratio, and shape fixity ratio of the test specimens were evaluated as a function of three CCF layout arrangements as well as fiber infill density embedded in Shape Memory Polymer (SMP) test specimens. The results revealed that the addition of CCF in the polymer matrix has a significant impact on shape memory behavior. Vertically aligned CCF in the SMP matrix improves the shape recovery ratio (92.97% compared to 78.77% of the pure SMP sample), while horizontal alignment of CCF ensures maximum shape fixity ratio (91.78% compared to 66.22% of the pure SMP sample). The cross-aligned CCF sample provides good recovery as well as fixity values. Further, it was observed that the horizontal alignment of CCF yields the fastest recovery performance. The outcome confirms that optimizing the fiber orientation enhances shape memory performance. Also, 40% of fiber infill density had greater shape fixity and overall recovery performance when compared to 30% and 50%. These findings have implications for tailored and high-performance SMPCs in biomedical devices, aerospace components, and robotics. Understanding temporal curvature behavior enables optimizing the design of materials with precise control over shape recovery. This research contributes to the design and optimization of SMPCs for diverse applications.

The repeatable among-individual variation in behavior (animal personality) is considered to affect fitness. The variation in personality traits is shaped by complex evolutionary mechanisms involving energy allocation and resource acquisition. However, an association between personality and individual performance in energy gain in the natural environment still seems underexplored. The aim of our study was to test a hypothesis that consistent individual variation in behavior affects the energy acquisition of unpredictable food resources. We predicted that more explorative individuals would be finding ephemeral food resources with higher probability than those less explorative. The quasi-experiment with ‘random-walking-feeders’ was performed to assess the use of unpredictable food resources in the natural habitat occupied by free-ranging arboreal rodents — edible dormice Glis glis. A repeated open field test at laboratory conditions was conducted to assess whether male dormice show consistent among-individual variation in behavior. The open field test analysis indicated two main components of dormice behavior: exploration and boldness, from which only the first one was repeatable and thus considered as a component of animal personality. The probability of finding a feeder increased with exploration, independently of dormice age and body size. The results indicate that exploration can be considered an adaptive trait that improves energy acquisition. We suggest that the behavioral among-individual variation within populations persists due to the usage of distinct foraging strategies in the face of fluctuations in food resources availability.

This work proposes an adaptive structure-preserving model order reduction method for finite-dimensional parametrized Hamiltonian systems modeling non-dissipative phenomena. To overcome the slowly decaying Kolmogorov width typical of transport problems, the full model is approximated on local reduced spaces that are adapted in time using dynamical low-rank approximation techniques. The reduced dynamics is prescribed by approximating the symplectic projection of the Hamiltonian vector field in the tangent space to the local reduced space. This ensures that the canonical symplectic structure of the Hamiltonian dynamics is preserved during the reduction. In addition, accurate approximations with low-rank reduced solutions are obtained by allowing the dimension of the reduced space to change during the time evolution. Whenever the quality of the reduced solution, assessed viaan error indicator, is not satisfactory, the reduced basis is augmented in the parameter direction that is worst approximated by the current basis. Extensive numerical tests involving wave interactions, nonlinear transport problems, and the Vlasov equation demonstrate the superior stability properties and considerable runtime speedups of the proposed method as compared to global and traditional reduced basis approaches.

The YAP/Hippo pathway is an organ growth and size regulation rheostat safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. Here, we report the identification and characterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi. NIBR-LTSi activates YAP signaling, shows good oral bioavailability, and expands organoids derived from several mouse and human tissues. In tissue stem cells, NIBR-LTSi promotes proliferation, maintains stemness, and blocks differentiation in vitroand in vivo. NIBR-LTSi accelerates liver regeneration following extended hepatectomy in mice. However, increased proliferation and cell dedifferentiation in multiple organs prevent prolonged systemic LATS inhibition, thus limiting potential therapeutic benefit. Together, we report a selective LATS kinase inhibitor agonizing YAP signaling and promoting tissue regeneration in vitroand in vivo, enabling future research on the regenerative potential of the YAP/Hippo pathway.

Drug-resistant pathogens pose a global challenge to public health as they cause diseases that are extremely difficult to cure. Metallo-β-lactamases (MBLs) are a diverse set of zinc-containing enzymes that catalyze the hydrolysis of β-lactam drugs, including carbapenems, which are considered as the last resort to fight severe infections. To restore the activity of current β-lactam antibiotics and to offer an orthogonal strategy to the discovery of new antibiotics, we have identified a series of polar N-aryl mercaptopropionamide derivatives as potent inhibitors of several class B1 MBLs. We have identified a hit structure with high selectivity restoring the effect of imipenem and reducing minimum inhibitory concentration (MIC) values up to 256-fold in resistant isolates from Escherichia coli. Furthermore, the combination of imipenem with our inhibitor showed in vivoefficacy in a Galleria mellonellamodel, increasing the survival rate of infected larvae by up to 31%.

Conjugated nanohoops incorporating nonalternant hydrocarbons have altered optoelectronic properties compared to [n]cycloparaphenylenes or other purely aromatic hoops. We synthesized [n]cyclo-1,5-dibenzopentalenes (n= 4, 5), in which nonalternant dibenzo[a,e]pentalenes are connected through their pentalene units. This leads to an increase in antiaromatic character and low-lying LUMO energies. Calculations show puckered or entangled conformations of the precursor macrocyclic Pt-complexes. Our study proves dibenzopentalene as a versatile nonalternant building block for conjugated nanohoops with modifiable antiaromaticity and optoelectronic properties.

Purpose: To assess the usefulness of water drinking test and dark room provocative testing (WDT + DRPT) in current clinical practice by evaluating input parameters from Swept-source Optical Coherence Tomography (SS-OCT) images, and to determine if clinical factors like axial length, central endothelial cell count (CECC) and retinal nerve fibre layer thickness (RNFL) thickness are associated with a positive WDT + DRPT. Methods: SS-OCT examination was performed in consecutive subjects presenting as new patients in the outpatient clinic aged > 40 years. If at least one eye met the inclusion criteria (anterior chamber angles &lt;20° and anterior chamber depth &lt; 2.5 mm on SS-OCT), subjects were included in this study and WDT + DRPT was carried out. The eye with the smallest angle was analysed. The difference in parameters between eyes with a positive (≥8 mmHg) and negative (&lt;8 mmHg) increase in intraocular pressure (IOP) after WDT + DRPT were statistically analysed. Second, the correlation between IOP increase after WDT + DRPT and anterior chamber angle parameters (RNFL thickness, CECC and axial length) was studied. Results: A total of 95 subjects with a mean age of 64 years were included. There was an association between IOP increase after WDT + DRPT and anterior chamber angle characteristics, however this was not of clinical significance. No positive results after WDT + DRPT were found in patients with anterior chamber angles ≥ 20°. Conclusions: The present findings indicate that this combined provocative test has no definite correlative or predictive value in angle closure disease. Further, the test is not useful in predicting early diagnosis or possible CECC or RNFL loss.

•ATM condylar orientation has been quantified using 3D modeling on 105 jaws.•Main results indicate that condyle location and orientation are highly significantly different between the left and right sides within the same mandible.•This morphologic study will enable further kinematic approches to better address the difference of motion representation observed for the right or left condyles.

Fractional operators are widely used in mathematical models describing abnormal and nonlocal phenomena. Although there are extensive numerical methods for solving the corresponding model problems, theoretical analysis such as the regularity result, or the relationship between the left-side and right-side fractional operators is seldom mentioned. Instead of considering the fractional derivative spaces, this paper starts from discussing the image spaces of Riemann-Liouville fractional integrals of Lp(Ω) functions, since the fractional derivative operators that are often used are all pseudo-differential. Then the high regularity situation-the image spaces of Riemann-Liouville fractional integral operators on the Wm,p(Ω) space is considered. Equivalent characterizations of the defined spaces, as well as those of the intersection of the left-side and right-side spaces are given. The behavior of the functions in the defined spaces at both the nearby boundary point/points and the points in the domain is demonstrated in a clear way. Besides, tempered fractional operators are shown to be reciprocal to the corresponding Riemann-Liouville fractional operators, which is expected to contribute some theoretical support for relevant numerical methods. Last, we also provide some instructions on how to take advantage of the introduced spaces when numerically solving fractional equations.

La pemphigoïde bulleuse (PB) atteint surtout les sujets âgés et le traitement de 1ère intention par dermocorticothérapie très forte (DCF) engendre des difficultés d’utilisation et des complications sur ce terrain. L’enjeu actuel est de réduire la durée et la quantité de DCF par un traitement facile d’emploi, sûr et permettant un contrôle durable. L’ustékinumab (UST) est un anticorps anti p40 indiqué dans des pathologies Th17 médiées, axe aussi impliqué dans la PB. Notre objectif était d’apporter la preuve de concept de l’efficacité de l’UST dans la PB.

In a recent dog study, the antibiotic metronidazole proved to be an effective disruptor of the fecal microbiota and resulted in looser stools and altered fecal bile acid (BA) profiles. Recovery took several weeks and was aided by a dietary supplement. The objective of this study was to determine how a veterinary gastrointestinal low-fat diet affected the fecal characteristics and metabolite, BA, and microbiota concentrations of dogs recovering from metronidazole administration. Twenty-four healthy adult dogs were used in an 8-wk completely randomized design study. The study began with a 2-wk baseline phase where all dogs consumed a leading grocery brand dry kibble diet (GBD; wk 0 to wk 2). Over the next 2 wk, dogs continued to consume GBD and received metronidazole (20 mg/kg BW; wk 2 to wk 4). At wk 4, dogs were randomly allotted to one of two treatments [GBD; Blue Buffalo Gastrointestinal Support Low-Fat (BB)] for the remaining 4 wk (wk 5 to wk 8). Fecal scores were recorded daily, and fresh fecal samples were collected at wk 2, 4, 5, 6, 7, and 8 for measurement of pH, dry matter, and metabolite and bile acid concentrations. Fecal microbiota populations were also analyzed by 16S rRNA sequencing and qPCR, which was used to calculate dysbiosis index. All data were analyzed as repeated measures using the Mixed Models procedure of SAS 9.4, with treatment treated as a fixed effect, dog as a random effect, and significance set at P< 0.05. As anticipated, metronidazole administration increased (P <0.0001) fecal scores (looser stools) and drastically altered (P <0.05) fecal metabolite concentrations, reducing fecal short-chain fatty acid (SCFA), branched-chain fatty acid (BCFA), phenol, and indole concentrations, increasing primary BA concentrations, and decreasing secondary bile acid concentrations. Metronidazole dramatically impacted fecal microbiota populations by reducing alpha diversity, altering the abundance of multiple bacterial taxa, and increasing dysbiosis index. Fecal outcome variables recovered over the next 4 wk, with some being impacted by diet. The change in fecal SCFA and immunoglobulin A concentrations were greater (P <0.01), while the change in fecal BCFA, phenol, and indole concentrations were decreased (P <0.05) in dogs fed BB. Dysbiosis index and alpha diversity measures recovered quickly for all dogs and without dietary effects. Recovery of over 25 bacterial genera were impacted by diet (P <0.05). While many bacterial taxa returned to baseline levels after 4 wk, others had still not fully recovered. Fecal BA concentrations recovered quickly for all dogs. The change in lithocholic acid concentration was less (P <0.0001) in dogs fed BB, but other BA concentrations were not affected by diet. In conclusion, metronidazole drastically alters the fecal microbiota and metabolites of dogs. While most variables return to normal over time, a veterinary gastrointestinal diet may aid in the recovery.

Antibiotics are often used to treat animals with gastrointestinal diseases or infections, but their use is known to have negative effects on the intestinal microbiota community. Identifying dietary strategies that may aid in the recovery from antibiotic use is of interest. The objective of this study was to determine how a veterinary gastrointestinal diet affected the fecal characteristics and metabolite, bile acid (BA), and microbiota concentrations of cats recovering from metronidazole administration. Twenty-four healthy adult cats were used in an 8-wk completely randomized design study. The study began with a 2-wk baseline phase where all cats consumed a leading grocery brand dry diet (GBD; wk 0 to wk 2). Over the next 2 wk, cats continued to consume GBD and received metronidazole (20 mg/kg BW; wk 2 to wk 4). At wk 4, cats were randomly allotted to one of two treatments [GBD; Blue Buffalo Gastrointestinal Support (BB)] for the remaining 4 wk (wk 5 to wk 8). Fecal scores were recorded daily, and fresh fecal samples were collected at wk 2, 4, 5, 6, 7, and 8 for measurement of pH, dry matter, and metabolite and BA concentrations. Fecal microbiota were analyzed by 16S rRNA sequencing and qPCR, which was used to calculate dysbiosis index. All data were analyzed as repeated measures using the Mixed Models procedure of SAS 9.4, with treatment treated as a fixed effect, cat as a random effect, and significance set at P< 0.05 and trends at P< 0.10. Metronidazole administration had dramatic effects on the outcomes measured, including increased fecal scores (looser stools), reduced fecal pH and dry matter %, reduced fecal short-chain fatty acid (SCFA), branched-chain fatty acid, ammonia, phenol, and indole concentrations, and altered fecal BA concentrations (increased primary BA; reduced secondary BA). Furthermore, fecal bacterial alpha diversity was reduced, dysbiosis index was increased, and the abundance of several individual bacterial taxa were altered. Fecal outcome variables partially recovered over the next 4 wk, with some being impacted by diet. The change in fecal acetate concentrations were greater and the change in total SCFA concentrations tended to be greater in cats fed BB. Dysbiosis index and alpha diversity measures slowly recovered over 4 wk, without differences due to diet. Recovery of about 20 bacterial genera were impacted by diet. Primary and secondary BA concentrations and ratios demonstrated a prolonged impairment of primary to secondary BA conversion. Most of these changes were an effect of time, but the change of fecal cholic acid concentrations were less in cats fed BB. In conclusion, our data demonstrate that metronidazole is a powerful antibiotic that has long-lasting effects on the fecal microbiota and metabolites of cats. The veterinary gastrointestinal diet tested aided in the recovery of some variables measured.