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1.
World Neurosurg X ; 23: 100308, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38584878

RESUMO

Background: There are no generally accepted criteria for selecting patients with recurrent glioblastoma for surgery. This retrospective study in a Danish population-based cohort aimed to identify prognostic factors affecting postoperative survival after repeated surgery for recurrent glioblastoma and to test if the preoperative New Scale for Recurrent Glioblastoma Surgery (NSGS) developed by Park CK et al could assist in the selection of patients for repeat glioblastoma surgery. Methods: Clinical data from 66 patients with recurrent glioblastoma and repeated surgery were analyzed. Kaplan-Meier plots were produced to illustrate survival in each of the three NSGS prognostic groups, and Cox proportional hazard regression was used to identify prognostic variables. Multivariable analysis was used to identify differences in survival in the three prognostic groups. Results: Six variables significantly affected postoperative survival: preoperative Karnofsky Performance Status (KPS) < 70 (p = 0.002), decreased KPS after second surgery (p = 0.012), ependymal involvement (p = 0.002), tumor volume â‰§ 50 cm3 (p = 0.021), age (p = 0.033) and Ki-67 (p = 0.005). Retrospective application of the criteria previously published by Park CK et al showed that median postoperative survival for the three prognostic groups was 390 days (0 points), 279 days (1 point), and 80 days (2 points), respectively. Conclusion: Several prognostic variables to predict postoperative survival in patients with recurrent glioblastoma were identified and should be considered when selecting patient for repeat surgery. The NSGS scoring system was useful as there were significant differences in postoperative survival between its three prognostic groups.

2.
Hepatology ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446707

RESUMO

BACKGROUND AIMS: High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort. APPROACH RESULTS: MMP-7 was measured in serum samples of 399 cholestatic infants in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p=0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved-fluorescence energy transfer (TR-FRET) assays. Discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an area under receiver operating curve (AUROC) of 0.90 (confidence interval [CI] 0.87-0.94). At cutoff 52.8 ng/mL, it produced sensitivity=94.03%, specificity=77.78%, positive predictive value=64.46%, and negative predictive value=96.82% for BA. AUROC for gamma-glutamyl transferase (GGT)=0.81 (CI 0.77-0.86), stool color=0.68 (CI 0.63-0.73), and pathology=0.84 (CI 0.76-0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+GGT AUROC to 0.91 (CI 0.88-0.95). Serum concentrations produced by TR-FRET differed from single-plex, with optimal cutoff of 18.2 ng/mL. Results were consistent within each assay technology and generated similar AUROCs. CONCLUSIONS: Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in evaluation of cholestatic infants may simplify diagnostic algorithms and shorten time to hepatoportoenterostomy.

3.
Nat Chem ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374454

RESUMO

The inimitable electronic structures of the lanthanide (Ln) ions are key to advanced materials and technologies involving these elements. The trivalent ions are ubiquitous and are used much more widely than the divalent and tetravalent analogues, which possess vastly different optical and magnetic properties. Hence, alteration of the valence electron count by external stimuli can lead to dramatic changes in materials properties. Compounds exhibiting a temperature-induced complete Ln(III) ⇄ Ln(II) switch, referred to as a valence tautomeric (VT) transition, are rare. Here we present an abrupt and hysteretic VT transition in a lanthanide-based coordination polymer, SmI2(pyrazine)3, driven by the interconversion of Sm(II)-pyrazine(0) and Sm(III)-pyrazine(·-) redox pairs. Alloying SmI2(pyrazine)3 with Yb(II) yields isomorphous Sm1-xYbxI2(pyrazine)3 solid solutions with VT transition critical temperatures ranging widely from 200 K to ∼50 K at ambient pressure. These findings demonstrate a simple strategy to realize thermally switchable magnetic materials with chemically tunable transition temperatures.

4.
Nat Commun ; 15(1): 1177, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331922

RESUMO

Acquiring spatial control of nanoscopic metal clusters is central to their function as efficient multi-electron catalysts. However, dispersing metal clusters on surfaces or in porous hosts is accompanied by an intrinsic heterogeneity that hampers detailed understanding of the chemical structure and its relation to reactivities. Tethering pre-assembled molecular metal clusters into polymeric, crystalline 2D or 3D networks constitutes an unproven approach to realizing ordered arrays of chemically well-defined metal clusters. Herein, we report the facile synthesis of a {Pd3} cluster-based organometallic framework from a molecular triangulo-Pd3(CNXyl)6 (Xyl = xylyl; Pd3) cluster under chemically mild conditions. The formally zero-valent Pd3 cluster readily engages in a complete ligand exchange when exposed to a similar, ditopic isocyanide ligand, resulting in polymerization into a 2D coordination network (Pd3-MOF). The structure of Pd3-MOF could be unambiguously determined by continuous rotation 3D electron diffraction (3D-ED) experiments to a resolution of ~1.0 Å (>99% completeness), showcasing the applicability of 3D-ED to nanocrystalline, organometallic polymers. Pd3-MOF displays Pd03 cluster nodes, which possess significant thermal and aerobic stability, and activity towards hydrogenation catalysis. Importantly, the realization of Pd3-MOF paves the way for the exploitation of metal clusters as building blocks for rigidly interlocked metal nanoparticles at the molecular limit.

5.
Pediatr Surg Int ; 40(1): 46, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294551

RESUMO

PURPOSE: Pilonidal disease (PD) is marked by chronic inflammation and frequent recurrence which can decrease quality of life. However, debate remains regarding the optimal treatment for PD in the pediatric population. This study compares two recommended treatment approaches-excision with off-midline flap reconstruction (OMF: Bascom cleft lift flap, modified Limberg flap) and minimally invasive endoscopic pilonidal sinus treatment (EPSiT). METHODS: Single-center retrospective evaluation of patients 1-21 years of age with PD who underwent either excision with OMF reconstruction or EPSiT between 10/1/2011 and 10/31/2021. Outcomes included were disease recurrence, reoperation, and wound complication rates. Comparisons were performed using Chi-square and Mann-Whitney U tests. RESULTS: 18 patients underwent excision/OMF reconstruction and 45 patients underwent EPSiT. The excision/OMF reconstruction cohort was predominantly male (44.4% vs 17.8% p = 0.028), with history of prior pilonidal infection (33.3% vs 6.7%; p = 0.006), and longer median operative time (60 min vs 17 min; p < 0.001). The excision/OMF reconstruction cohort had a higher rate of wound complications (22.2% vs 0%; p = 0.001), but lower rates of disease recurrence (5.6% vs 33.3%; p = 0.022) and reoperation (5.6% vs 31.1%; p = 0.031). CONCLUSION: In pediatric patients with PD, excision with OMF reconstruction may decrease recurrence and reoperation rates with increased operative times and wound complication rates, compared to EPSiT.


Assuntos
Seio Pilonidal , Dermatopatias , Humanos , Criança , Masculino , Feminino , Seio Pilonidal/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Endoscopia , Reoperação
6.
ESMO Open ; 9(1): 102219, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38194881

RESUMO

BACKGROUND: Despite the prognostic relevance of cachexia in pancreatic cancer, individual body composition has not been routinely integrated into treatment planning. In this multicenter study, we investigated the prognostic value of sarcopenia and myosteatosis automatically extracted from routine computed tomography (CT) scans of patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed clinical imaging data of 601 patients from three German cancer centers. We applied a deep learning approach to assess sarcopenia by the abdominal muscle-to-bone ratio (MBR) and myosteatosis by the ratio of abdominal inter- and intramuscular fat to muscle volume. In the pooled cohort, univariable and multivariable analyses were carried out to analyze the association between body composition markers and overall survival (OS). We analyzed the relationship between body composition markers and laboratory values during the first year of therapy in a subgroup using linear regression analysis adjusted for age, sex, and American Joint Committee on Cancer (AJCC) stage. RESULTS: Deep learning-derived MBR [hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.47-0.77, P < 0.005] and myosteatosis (HR 3.73, 95% CI 1.66-8.39, P < 0.005) were significantly associated with OS in univariable analysis. In multivariable analysis, MBR (P = 0.019) and myosteatosis (P = 0.02) were associated with OS independent of age, sex, and AJCC stage. In a subgroup, MBR and myosteatosis were associated with albumin and C-reactive protein levels after initiation of therapy. Additionally, MBR was also associated with hemoglobin and total protein levels. CONCLUSIONS: Our work demonstrates that deep learning can be applied across cancer centers to automatically assess sarcopenia and myosteatosis from routine CT scans. We highlight the prognostic role of our proposed markers and show a strong relationship with protein levels, inflammation, and anemia. In clinical practice, automated body composition analysis holds the potential to further personalize cancer treatment.


Assuntos
Aprendizado Profundo , Neoplasias Pancreáticas , Sarcopenia , Humanos , Prognóstico , Sarcopenia/complicações , Músculo Esquelético/patologia , Estudos Retrospectivos , Composição Corporal , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia
7.
Acta Anaesthesiol Scand ; 68(4): 546-555, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38267221

RESUMO

The DEXamethasone twice for pain treatment after Total Knee Arthroplasty (DEX-2-TKA) trial showed that adding one and two doses of 24 mg intravenous dexamethasone to paracetamol, ibuprofen and local infiltration analgesia, reduced morphine consumption (primary outcome) within 48 h after TKA. We aimed to explore the differences in the effect of dexamethasone on morphine consumption in different subgroups. Quantile regression adjusted for site was used to test for significant interaction between the predefined dichotomised subgroups and treatment group. The subgroups were defined based on baseline data: sex (male/female), age (≤65 years/>65 years), American Society of Anaesthesiologists (ASA)-score (ASA I + II/III), visual analogue score of preoperative pain at rest (≤30 mm/>30 mm), pain during mobilisation (≤30 mm/>30 mm), type of anaesthesia (spinal anaesthesia/general anaesthesia and spinal converted to general anaesthesia), and prior daily use of analgesics (either paracetamol and/or NSAID/neither). These analyses were supplemented with post hoc multivariate linear regression analyses. Test of interaction comparing sex in the pairwise comparison between DX2 (dexamethasone [24 mg] + dexamethasone [24 mg]) versus placebo (p = .02), showed a larger effect of dexamethasone on morphine consumption in male patients compared to females. Test of interaction comparing age in the pairwise comparison between DX1 (dexamethasone [24 mg] + placebo) versus placebo (p = .04), showed a larger effect of dexamethasone on morphine consumption in younger patients (≤65 years) compared to older. All remaining subgroup analyses showed no evidence of a difference. The supplemental multivariate analyses did not support any significant interaction for sex (p = .256) or age (p = .730) but supported a significant interaction with the type of anaesthesia (p < .001). Our results from the quantile regression analyses indicate that the male sex and younger age (≤65 years) may be associated with a larger analgesic effect of dexamethasone than the effects in other types of patients. However, this is not supported by post-hoc multivariate linear regression analyses. The two types of analyses both supported a possible interaction with the type of anaesthesia.


Assuntos
Artroplastia do Joelho , Morfina , Humanos , Masculino , Feminino , Idoso , Morfina/uso terapêutico , Acetaminofen/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dexametasona/uso terapêutico , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego
8.
ACS Sens ; 8(9): 3478-3486, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37669038

RESUMO

The detection of methane and carbon dioxide is of growing importance due to their negative impact on global warming. This is true for both environmental monitoring and leak detection in industrial processes. Although solid-state sensors are technologically mature, they have limitations that prohibit their use in certain situations, e.g., explosive atmospheres. Thus, there is a need to develop new types of sensor materials. Herein, we demonstrate a simple, low-cost, metal-organic framework (MOF)-based gas leak detection sensor. The system is based on gravimetric sensing by using a quartz crystal microbalance. The quartz crystal is functionalized by layer-by-layer growth of a thin metal-organic framework film. This film shows selective uptake of methane or carbon dioxide under atmospheric conditions. The hardware has low cost, simple operation, and theoretically high sensitivity. Overall, the sensor is characterized by simplicity and high robustness. Furthermore, by exploiting the different adsorption kinetics as measured by multiple harmonic analyses, it is possible to discriminate whether the response is due to methane or carbon dioxide. In summary, we demonstrate data relevant toward new applications of metal-organic frameworks and microporous hybrid materials in sensing.


Assuntos
Dióxido de Carbono , Estruturas Metalorgânicas , Temperatura , Adsorção , Metano
9.
Phys Chem Chem Phys ; 25(35): 23417-23434, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37486006

RESUMO

We apply ultrashort X-ray laser pulses to track optically excited structural dynamics of [Ir2(dimen)4]2+ molecules in solution. In our exploratory study we determine angular correlations in the scattered X-rays, which comprise a complex fingerprint of the ultrafast dynamics. Model-assisted analysis of the experimental correlation data allows us to elucidate various aspects of the photoinduced changes in the excited molecular ensembles. We unambiguously identify that in our experiment the photoinduced transition dipole moments in [Ir2(dimen)4]2+ molecules are oriented perpendicular to the Ir-Ir bond. The analysis also shows that the ground state conformer of [Ir2(dimen)4]2+ with a larger Ir-Ir distance is mostly responsible for the formation of the excited state. We also reveal that the ensemble of solute molecules can be characterized with a substantial structural heterogeneity due to solvent influence. The proposed X-ray correlation approach offers an alternative path for studies of ultrafast structural dynamics of molecular ensembles in the liquid and gas phases.

10.
J Arthroplasty ; 38(12): 2592-2598.e2, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37286048

RESUMO

BACKGROUND: Perioperative dexamethasone as an adjunct to multimodal analgesia, has an opioid-sparing and pain alleviating effect after total knee arthroplasty (TKA), however, the 3-year effects are unknown. We aimed to investigate the 3-year effect of 1 (DX1) or 2 (DX2) intravenous doses of 24 mg dexamethasone or placebo on pain, physical function, and health-related quality of life after TKA. METHODS: Patients who participated in the Dexamethasone Twice for Pain Treatment after TKA (DEX-2-TKA) were invited to physical tests and questionnaires (self-reported characteristics, Oxford Knee Score, EuroQol-5Dimensions-5Levels (EQ5D5L), and PainDetect). The tests were 40-meter Fast Paced Walk (40FPW) test, Timed Up and Go (TUG), 30 Second Chair Stand test (30CST), Stair Climb Test (SCT), bilateral knee Range of Motion, and knee extension torque. For each test the peak pain intensity was registered on a 0 to 100 mm Visual Analogue Scale. Primary outcome was average peak pain intensity during the 40FPW, TUG, 30CST and SCT. Secondary outcomes were the tests and questionnaires. Out of 252 eligible patients, 133 (52.8%) underwent the tests and 160 (63.5%) answered the questionnaires. Mean follow-up time was 33 months (range, 23 to 40). RESULTS: Median (interquartile range) peak pain intensity was 0 (0 to 65) for the DX2 group, 0 (0 to 51) for DX1 group and 0 (0 to 70) for the placebo group (P = .72). No differences in secondary outcomes were identified. CONCLUSION: One or 2 intravenous doses of 24 mg dexamethasone did not impact chronic pain development or physical function 3 years after TKA.


Assuntos
Artroplastia do Joelho , Dor Crônica , Humanos , Artroplastia do Joelho/efeitos adversos , Seguimentos , Qualidade de Vida , Dexametasona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle
11.
Nat Commun ; 14(1): 3408, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296135

RESUMO

Control of magnetization and electric polarization is attractive in relation to tailoring materials for data storage and devices such as sensors or antennae. In magnetoelectric materials, these degrees of freedom are closely coupled, allowing polarization to be controlled by a magnetic field, and magnetization by an electric field, but the magnitude of the effect remains a challenge in the case of single-phase magnetoelectrics for applications. We demonstrate that the magnetoelectric properties of the mixed-anisotropy antiferromagnet LiNi1-xFexPO4 are profoundly affected by partial substitution of Ni2+ ions with Fe2+ on the transition metal site. This introduces random site-dependent single-ion anisotropy energies and causes a lowering of the magnetic symmetry of the system. In turn, magnetoelectric couplings that are symmetry-forbidden in the parent compounds, LiNiPO4 and LiFePO4, are unlocked and the dominant coupling is enhanced by almost two orders of magnitude. Our results demonstrate the potential of mixed-anisotropy magnets for tuning magnetoelectric properties.


Assuntos
Eletricidade , Campos Magnéticos , Anisotropia , Imãs
12.
ESMO Open ; 8(3): 101539, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37148593

RESUMO

BACKGROUND: Pancreatic cancer has a dismal prognosis. One reason is resistance to cytotoxic drugs. Molecularly matched therapies might overcome this resistance but the best approach to identify those patients who may benefit is unknown. Therefore, we sought to evaluate a molecularly guided treatment approach. MATERIALS AND METHODS: We retrospectively analyzed the clinical outcome and mutational status of patients with pancreatic cancer who received molecular profiling at the West German Cancer Center Essen from 2016 to 2021. We carried out a 47-gene DNA next-generation sequencing (NGS) panel. Furthermore, we assessed microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status and, sequentially and only in case of KRAS wild-type, gene fusions via RNA-based NGS. Patient data and treatment were retrieved from the electronic medical records. RESULTS: Of 190 included patients, 171 had pancreatic ductal adenocarcinoma (90%). One hundred and three patients had stage IV pancreatic cancer at diagnosis (54%). MMR analysis in 94 patients (94/190, 49.5%) identified 3 patients with dMMR (3/94, 3.2%). Notably, we identified 32 patients with KRAS wild-type status (16.8%). To identify driver alterations in these patients, we conducted an RNA-based fusion assay on 13 assessable samples and identified 5 potentially actionable fusions (5/13, 38.5%). Overall, we identified 34 patients with potentially actionable alterations (34/190, 17.9%). Of these 34 patients, 10 patients (10/34, 29.4%) finally received at least one molecularly targeted treatment and 4 patients had an exceptional response (>9 months on treatment). CONCLUSIONS: Here, we show that a small-sized gene panel can suffice to identify relevant therapeutic options for pancreatic cancer patients. Informally comparing with previous large-scale studies, this approach yields a similar detection rate of actionable targets. We propose molecular sequencing of pancreatic cancer as standard of care to identify KRAS wild-type and rare molecular subsets for targeted treatment strategies.


Assuntos
Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Estudos Retrospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Genômica , Neoplasias Pancreáticas
13.
Hepatol Commun ; 7(6)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37184518

RESUMO

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH. METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes. RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. Patients with ALF were younger [median 0.8 y (range, 0.0, 9.4) vs 3.4 y (0.2, 18.6), p < 0.001] with fewer neurodevelopmental delays (40.0% vs 81.3%, p < 0.001) versus Chronic. Comprehensive testing was performed more often in Chronic than ALF (90.0% vs 43.2%); however, etiology was identified more often in ALF (81.3% vs 61.1%) with mtDNA depletion being most common (ALF: 77% vs Chronic: 41%). Of the sequenced cohort (n = 60), 63% had an identified mitochondrial disorder. Cluster analysis identified a subset without an underlying genetic etiology, despite comprehensive testing. Liver transplant-free survival was 40% at 2 years (ALF vs Chronic, 16% vs 65%, p < 0.001). Eighteen (21%) underwent transplantation. With 33 patient-years of follow-up after the transplant, 3 deaths were reported. CONCLUSIONS: Differences between ALF and Chronic MH phenotypes included age at diagnosis, systemic involvement, transplant-free survival, and genetic etiology, underscoring the need for ultra-rapid sequencing in the appropriate clinical setting. Cluster analysis revealed a group meeting enrollment criteria but without an identified genetic or enzymatic diagnosis, highlighting the need to identify other etiologies.


Assuntos
Falência Hepática Aguda , Transplante de Fígado , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/genética , Transplante de Fígado/efeitos adversos , DNA Mitocondrial/genética , Fenótipo
15.
J Acoust Soc Am ; 153(3): 1554, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37002091

RESUMO

We revisit the problem of constructing one-dimensional acoustic black holes. Instead of considering the Euler-Bernoulli beam theory, we use Timoshenko's approach, which is known to be more realistic at higher frequencies. Our goal is to minimize the reflection coefficient under a constraint imposed on the normalized wavenumber variation. We use the calculus of variations to derive the corresponding Euler-Lagrange equation analytically and then use numerical methods to solve this equation to find the "optimal" height profile for different frequencies. We then compare these profiles to the corresponding ones previously found using the Euler-Bernoulli beam theory and see that in the lower range of the dimensionless frequency Ω (defined using the largest height of the plate), the optimal profiles almost coincide, as expected.

16.
Hepatol Commun ; 7(2): e0018, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662671

RESUMO

BACKGROUND AND AIMS: Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. APPROACH AND RESULTS: Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. CONCLUSIONS: We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.


Assuntos
Ductos Biliares Extra-Hepáticos , Colestase , Animais , Camundongos , Antígeno AC133/genética , Fígado , Epitélio , Fatores de Transcrição
17.
Chem Commun (Camb) ; 59(12): 1609-1612, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36692932

RESUMO

Self-assembly of trans-{EuI2} nodes and ditopic ligands leads to isoreticular 2D frameworks featuring a rare, non-kagome Archimedean tessellation. The topology and intra-layer Eu(II)-Eu(II) antiferromagnetic interactions provide the prerequisites for geometrical spin frustration, which, due to the spin state degeneracy, is key for novel phenomena such as enhanced magnetic refrigeration.

18.
Hepatology ; 77(5): 1639-1653, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36626628

RESUMO

BACKGROUND AND AIMS: Biliary atresia (BA), a congenital cholestatic liver disease, commonly culminates in end-stage liver disease. We previously demonstrated in BA that Prominin-1 ( Prom1 )-expressing hepatic progenitor cells (HPCs) expand within regions of developing fibrosis, giving rise to cholangiocytes within biliary ductular reactions. Null mutation of Prom1 or ablation of cells expressing Prom1 significantly diminishes fibrogenesis. FN14, the receptor for TNF-like weak inducer of apoptosis (TWEAK), is expressed by HPCs. TWEAK/FN14 signaling promotes fibrosis in multiple organ systems. Therefore, we hypothesized that TWEAK/FN14 signaling mediates Prom1 -expressing HPC proliferation leading to profibrogenic ductular reactions in BA. APPROACH AND RESULTS: The experimental mouse model of BA mediated by perinatal rhesus rotavirus (RRV) infection resulted in increased co-expression of Fn14 in Prom1 -expressing HPCs within regions of ductular reactions. FN14 antagonist L524-0366 decreased ductular reactions, biliary fibrosis and periportal fibroblast activation in RRV injury. L524-0366 inhibition also demonstrated loss of downstream noncanonical NF-kB signaling expression in RRV injury. Murine HPC organoids demonstrated accelerated organoid growth and proliferation when treated with recombinant TWEAK. Increased organoid proliferation with recombinant TWEAK was lost when also treated with L524-0366. Analysis of a large publicly available RNA sequencing database of BA and normal control patients revealed significant increases in expression of PROM1 , FN14 , and genes downstream of TNF signaling and noncanonical NF-κB signaling pathways in BA infants. Infants who failed to achieve bile drainage after hepatoportoenterostomy had higher relative levels of FN14 expression. CONCLUSION: TWEAK/FN14 signaling activation in Prom1 -expressing HPCs contributes to proliferation of profibrogenic ductular reactions in BA.


Assuntos
Atresia Biliar , Infecções por Rotavirus , Rotavirus , Animais , Camundongos , Antígeno AC133/genética , Atresia Biliar/metabolismo , Fibrose , Rotavirus/metabolismo , Células-Tronco/metabolismo , Fatores de Transcrição , Fatores de Necrose Tumoral/metabolismo , Fatores de Necrose Tumoral/farmacologia
19.
Phys Chem Chem Phys ; 25(4): 3309-3322, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36630169

RESUMO

The magnetic properties of the nickelalumite-type layered double hydroxides (LDH), MAl4(OH)12(SO4)·3H2O (MAl4-LDH) with M = Co2+ (S = 3/2), Ni2+ (S = 1), or Cu2+ (S = 1/2) were determined by a combined experimental and computational approach. They represent three new inorganic, low-dimensional magnetic systems with a defect-free, structurally ordered magnetic lattice. They exhibit no sign of magnetic ordering down to 2 K in contrast to conventional hydrotalcite LDH. Detailed insight into the complex interplay between the choice of magnetic ion (M2+) and magnetic properties was obtained by a combination of magnetic susceptibility, heat capacity, neutron scattering, solid-state NMR spectroscopy, and first-principles calculations. The NiAl4- and especially CoAl4-LDH have pronounced zero-field splitting (ZFS, easy-axis and easy-plane, respectively) and weak ferromagnetic nearest-neighbour interactions. Thus, they are rare examples of predominantly zero-dimensional spin systems in dense, inorganic matrices. In contrast, CuAl4-LDH (S = 1/2) consists of weakly ferromagnetic S = 1/2 spin chains. For all three MAl4-LDH, good agreement is found between the experimental magnetic parameters (J, D, g) and first-principles quantum chemical calculations, which also predict that the interchain couplings are extremely weak (< 0.1 cm-1). Thus, our approach will be valuable for evaluation and prediction of magnetic properties in other inorganic materials.

20.
J Pediatr Surg ; 58(1): 45-51, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36289033

RESUMO

PURPOSE: Surgical site infection (SSI) remains a significant source of patient morbidity and resource utilization in children undergoing colorectal surgery. We examined the utility of a protocolized perioperative care bundle in reducing SSI in pediatric patients undergoing colorectal surgery. METHODS: We conducted a prospective cohort study of patients ≤18 years of age undergoing colorectal surgery at ten United States children's hospitals. Using a perioperative care protocol comprising eight elements, or "colon bundle", we divided patients into low (1-4 elements) or high (5-8 elements) compliance cohorts. Procedures involving colorectal repair or anastomosis with abdominal closure were included. Demographics and clinical outcomes were compared between low and high compliance cohorts. Compliance was compared with a retrospective cohort. The primary outcome was superficial SSI incidence at 30 days. RESULTS: Three hundred and thirty-six patients were included in our analysis: 138 from the low compliance cohort and 198 from the high compliance cohort. Age and gender were similar between groups. Preoperative diagnosis was similar except for more patients in the high compliance cohort having inflammatory bowel disease (18.2% versus 5.8%, p<0.01). The most common procedure performed was small bowel to colorectal anastomosis. Wound classification and procedure acuity were similar between groups. Superficial SSI at 30 days occurred less frequently among the high compliance compared to the low compliance cohort (4% versus 9.7%, p = 0.036). Median postoperative length of stay and 30-day rates of readmission, reoperation, intra-abdominal abscess and anastomotic leak requiring operation were not significantly different between groups. None of the individual colon bundle elements were independently protective against superficial SSI. CONCLUSION: Standardization of perioperative care is associated with a reduction in superficial SSI in pediatric colorectal surgery. Expansion of standardized protocols for children undergoing colorectal surgery may improve outcomes and decrease perioperative morbidity. TYPE OF STUDY: Clinical Research Paper LEVEL OF EVIDENCE: Level II.


Assuntos
Neoplasias Colorretais , Assistência Perioperatória , Infecção da Ferida Cirúrgica , Criança , Humanos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Assistência Perioperatória/métodos , Estudos Prospectivos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/etiologia , Complicações Pós-Operatórias
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