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1.
Microvasc Res ; 151: 104596, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37625620

RESUMEN

In the later stages of angiogenesis, the vascular sprout transitions into a functional vessel by fusing with a target vessel. Although this process appears to routinely occur in embryonic tissue, the biologic rules for sprout fusion and lumenization in adult regenerating tissue are unknown. To investigate this process, we grafted portions of the regenerating post-pneumonectomy lung onto the chick chorioallantoic membrane (CAM). Grafts from all 4 lobes of the post-pneumonectomy right lung demonstrated peri-graft angiogenesis as reflected by fluorescent plasma markers; however, fluorescent microsphere perfusion primarily occurred in the lobe of the lung that is the dominant site of post-pneumonectomy angiogenesis-namely, the cardiac lobe. Vascularization of the cardiac lobe grafts was confirmed by active tissue growth (p < .05). Functional vascular connections between the cardiac lobe and the CAM vascular network were demonstrated by confocal fluorescence microscopy as well as corrosion casting and scanning electron microscopy (SEM). Bulk transcriptional profiling of the cardiac lobe demonstrated the enhanced expression of many genes relative to alveolar epithelial cell (CD11b-/CD31-) control cells, but only the upregulation of Ereg and Fgf6 compared to the less well-vascularized right upper lobe. The growth of actively regenerating non-neoplastic adult tissue on the CAM demonstrates that functional lumenization can occur between species (mouse and chick) and across the developmental spectrum (adult and embryo).


Asunto(s)
Membrana Corioalantoides , Neovascularización Fisiológica , Ratones , Animales , Membrana Corioalantoides/irrigación sanguínea , Pollos , Neovascularización Patológica , Pulmón
2.
J Surg Res ; 295: 61-69, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37992454

RESUMEN

INTRODUCTION: Neoadjuvant chemoradiation therapy (NCRT) for cT1b esophageal cancer is not recommended despite the risk of pathologic upstaging with increased depth of penetration. We aimed to (1) define the rate of and factors associated with pathologic upstaging, (2) describe current trends in treatments, and (3) compare overall survival (OS) with and without NCRT for surgically resected cT1b lesions. METHODS: We used the 2020 National Cancer Database to identify patients with cT1b N0 esophageal cancer with or without pathologic upstaging who underwent removal of their tumor. We built multivariable logistic regression models to assess factors associated with pathologic upstaging. Survival was compared using log-rank analysis and modeled using multivariable Cox proportional hazards regressions. RESULTS: Out of 1106 patients with cT1b esophageal cancer, 17.3% (N = 191) had pathologic upstaging. A higher tumor grade (P = 0.002), greater tumor size (P < 0.001), and presence of lympho-vascular invasion (P < 0.001) were associated with pathologic upstaging. 8.0% (N = 114) of patients were treated with NCRT. Five-y OS was 49.4% for patients who received NCRT compared to 67.2% for upfront esophagectomy (P < 0.05). Pathologic upstaging was associated with decreased OS (pathologic upstaging 43.7% versus no pathologic upstaging 67.7%) (hazard ratio 2.12 [95% confidence interval, 1.70-2.65; P < 0.001]). Compared to esophagectomy, endoscopic local tumor excision was associated with a decreased OS (hazard ratio 1.50 [95% confidence interval, 1.19-1.89; P = 0.001]). CONCLUSIONS: Pathologic upstaging of cT1b lesions is associated with decreased OS. Esophagectomy is associated with a survival benefit over endoscopic local tumor excision for these lesions. NCRT is not associated with an increase in OS in cT1b lesions compared to upfront esophagectomy.


Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Humanos , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Esofágicas/cirugía , Adenocarcinoma/cirugía , Esofagectomía , Estudios Retrospectivos , Resultado del Tratamiento
3.
J Immunol ; 208(6): 1362-1370, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35228263

RESUMEN

The oncotherapeutic promise of IL-15, a potent immunostimulant, is limited by a short serum t 1/2 The fusion protein N-803 is a chimeric IL-15 superagonist that has a >20-fold longer in vivo t 1/2 versus IL-15. This phase 1 study characterized the pharmacokinetic (PK) profile and safety of N-803 after s.c. administration to healthy human volunteers. Volunteers received two doses of N-803, and after each dose, PK and safety were assessed for 9 d. The primary endpoint was the N-803 PK profile, the secondary endpoint was safety, and immune cell levels and immunogenicity were measures of interest. Serum N-803 concentrations peaked 4 h after administration and declined with a t 1/2 of ∼20 h. N-803 did not cause treatment-emergent serious adverse events (AEs) or grade ≥3 AEs. Injection site reactions, chills, and pyrexia were the most common AEs. Administration of N-803 was well tolerated and accompanied by proliferation of NK cells and CD8+ T cells and sustained increases in the number of NK cells. Our results suggest that N-803 administration can potentiate antitumor immunity.


Asunto(s)
Linfocitos T CD8-positivos , Interleucina-15 , Voluntarios Sanos , Humanos , Proteínas Recombinantes de Fusión
4.
Macromol Rapid Commun ; 45(1): e2300219, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37277618

RESUMEN

Non-conjugated pendant electroactive polymers (NCPEPs) are an emerging class of polymers that offer the potential of combining the desirable optoelectronic properties of conjugated polymers with the superior synthetic methodologies and stability of traditional non-conjugated polymers. Despite an increasing number of studies focused on NCPEPs, particularly on understanding fundamental structure-property relationships, no attempts have been made to provide an overview on established relationships to date. This review showcases selected reports on NCPEP homopolymers and copolymers that demonstrate how optical, electronic, and physical properties of the polymers are affected by tuning of key structural variables such as the chemical structure of the polymer backbone, molecular weight, tacticity, spacer length, the nature of the pendant group, and in the case of copolymers the ratios between different comonomers and between individual polymer blocks. Correlation of structural features with improved π-stacking and enhanced charge carrier mobility serve as the primary figures of merit in evaluating impact on NCPEP properties. While this review is not intended to serve as a comprehensive summary of all reports on tuning of structural parameters in NCPEPs, it highlights relevant established structure-property relationships that can serve as a guideline for more targeted design of novel NCPEPs in the future.


Asunto(s)
Electrónica , Polímeros , Polímeros/química , Electrónica/métodos , Peso Molecular
5.
J Am Chem Soc ; 145(22): 11914-11920, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37220423

RESUMEN

Designing new polymer semiconductors for intrinsically stretchable polymer solar cells (IS-PSCs) with high power conversion efficiency (PCE) and durability is critical for wearable electronics applications. Nearly all high-performance PSCs are constructed using fully conjugated polymer donors (PD) and small-molecule acceptors (SMA). However, a successful molecular design of PDs for high-performance and mechanically durable IS-PSCs without sacrificing conjugation has not been realized. In this study, we design a novel thymine side chain terminated 6,7-difluoro-quinoxaline (Q-Thy) monomer and synthesize a series of fully conjugated PDs (PM7-Thy5, PM7-Thy10, PM7-Thy20) featuring Q-Thy. The Q-Thy units capable of inducing dimerizable hydrogen bonding enable strong intermolecular PD assembly and highly efficient and mechanically robust PSCs. The PM7-Thy10:SMA blend demonstrates a combination of high PCE (>17%) in rigid devices and excellent stretchability (crack-onset value >13.5%). More importantly, PM7-Thy10-based IS-PSCs show an unprecedented combination of PCE (13.7%) and ultrahigh mechanical durability (maintaining 80% of initial PCE after 43% strain), illustrating the promising potential for commercialization in wearable applications.

6.
Ann Surg ; 278(4): 609-620, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37334722

RESUMEN

OBJECTIVES: To summarize waitlist and transplant outcomes in kidney, liver, lung, and heart transplantation using organ donation after circulatory death (DCD). BACKGROUND: DCD has expanded the donor pool for solid organ transplantation, most recently for heart transplantation. METHODS: The United Network for Organ Sharing registry was used to identify adult transplant candidates and recipients in the most recent allocation policy eras for kidney, liver, lung, and heart transplantation. Transplant candidates and recipients were grouped by acceptance criteria for DCD versus brain-dead donors [donation after brain death (DBD)] only and DCD versus DBD transplant, respectively. Propensity matching and competing-risks regression was used to model waitlist outcomes. Survival was modeled using propensity matching and Kaplan-Meier and Cox regression analysis. RESULTS: DCD transplant volumes have increased significantly across all organs. Liver candidates listed for DCD organs were more likely to undergo transplantation compared with propensity-matched candidates listed for DBD only, and heart and liver transplant candidates listed for DCD were less likely to experience death or clinical deterioration requiring waitlist inactivation. Propensity-matched DCD recipients demonstrated an increased mortality risk up to 5 years after liver and kidney transplantation and up to 3 years after lung transplantation compared with DBD. There was no difference in 1-year mortality between DCD and DBD heart transplantation. CONCLUSIONS: DCD continues to expand access to transplantation and improves waitlist outcomes for liver and heart transplant candidates. Despite an increased risk for mortality with DCD kidney, liver, and lung transplantation, survival with DCD transplant remains acceptable.


Asunto(s)
Trasplante de Hígado , Trasplante de Órganos , Obtención de Tejidos y Órganos , Adulto , Humanos , Estados Unidos , Resultado del Tratamiento , Donantes de Tejidos , Muerte Encefálica , Supervivencia de Injerto , Estudios Retrospectivos , Muerte
7.
Phys Rev Lett ; 131(8): 080801, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37683172

RESUMEN

Device-independent quantum key distribution (DIQKD) is information-theoretically secure against adversaries who possess a scalable quantum computer and who have supplied malicious key-establishment systems; however, the DIQKD key rate is currently too low. Consequently, we devise a DIQKD scheme based on the quantum nonlocal Mermin-Peres magic square game: our scheme asymptotically delivers DIQKD against collective attacks, even with noise. Our scheme outperforms DIQKD using the Clauser-Horne-Shimony-Holt game with respect to the number of game rounds, albeit not number of entangled pairs, provided that both state visibility and detection efficiency are high enough.

8.
Phys Rev Lett ; 131(13): 133601, 2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37831993

RESUMEN

Berry curvature is a fundamental element to characterize topological quantum physics, while a full measurement of Berry curvature in momentum space was not reported for topological states. Here we achieve two-dimensional Berry curvature reconstruction in a photonic quantum anomalous Hall system via Hall transport measurement of a momentum-resolved wave packet. Integrating measured Berry curvature over the two-dimensional Brillouin zone, we obtain Chern numbers corresponding to -1 and 0. Further, we identify bulk-boundary correspondence by measuring topology-linked chiral edge states at the boundary. The full topological characterization of photonic Chern bands from Berry curvature, Chern number, and edge transport measurements enables our photonic system to serve as a versatile platform for further in-depth study of novel topological physics.

9.
Phys Rev Lett ; 129(4): 046401, 2022 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-35939012

RESUMEN

Topological insulators host topology-linked boundary states, whose spin and charge degrees of freedom could be exploited to design topological devices with enhanced functionality. We experimentally observe that dissipationless chiral edge states in a spin-orbit coupled anomalous Floquet topological phase exhibit topological spin texture on boundaries, realized via a two-dimensional quantum walk. Our experiment shows that, for a walker traveling around a closed loop along the boundary in real space, its spin evolves and winds through a great circle on the Bloch sphere, which implies that edge-spin texture has nontrivial winding. This topological spin winding is protected by a chiral-like symmetry emerging for the low-energy Hamiltonian. Our experiment confirms that two-dimensional anomalous Floquet topological systems exhibit topological spin texture on the boundary, which could inspire novel topology-based spintronic phenomena and devices.

10.
Scand J Gastroenterol ; 57(7): 807-813, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35188055

RESUMEN

BACKGROUND AND AIM: Refractory bowel symptoms in quiescent inflammatory bowel disease (IBD) are common but evidence for effective management is limited. We aimed to determine whether behavioral treatment, including pelvic floor muscle training, decreases the severity of functional bowel symptoms in patients with quiescent IBD. Secondary aims were to evaluate the treatment effect on quality of life, psychological well-being and pelvic floor muscle function. METHODS: This prospective study included IBD patients in remission with persistent symptoms of fecal incontinence or constipation who received up to six sessions of behavioral treatment at monthly intervals. The primary outcome was patient-rated symptom improvement on a 7-point Likert scale (1 = substantially worse, 7 = substantially better). Secondary outcomes included validated symptom scores, quality-of-life, psychological measures, and transperineal ultrasound assessment of pelvic floor muscle activity. RESULTS: Thirty-four patients (median age 38 years; 24 females; 18 ulcerative colitis, 13 Crohn's disease, 3 ileo-anal pouch) were included. Twenty-one of the 29 (72%) patients who completed treatment, or 21 of all 34 (62%) patients, reported moderate or substantial improvement (patient rating of 6 or 7). Symptom scores (p < .001), IBD-specific quality of life (p = .008) and illness perception scores (p = .003) significantly improved. General quality of life, and anxiety and depression scores, did not change significantly. Transperineal ultrasound pelvic floor measures did not correlate with patient-rating of symptom improvement. CONCLUSION: Significant symptomatic improvement occurred in a majority of patients with quiescent IBD. Behavioral treatment should be considered for patients with quiescent IBD and ongoing functional bowel symptoms of fecal incontinence, fecal urgency, or constipation.


Asunto(s)
Incontinencia Fecal , Enfermedades Inflamatorias del Intestino , Adulto , Enfermedad Crónica , Estreñimiento/etiología , Estreñimiento/terapia , Incontinencia Fecal/etiología , Incontinencia Fecal/terapia , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/terapia , Diafragma Pélvico/diagnóstico por imagen , Estudios Prospectivos , Calidad de Vida
11.
Clin Med Res ; 20(2): 81-88, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35086853

RESUMEN

Objective: Many clinical microbiology laboratories procure antimicrobial susceptibility testing data using guidelines established by Clinical and Laboratory Standards Institute (CLSI). When necessary, CLSI revises interpretive breakpoints in efforts to improve clinical correlation, with two revisions relative to fluoroquinolone agents occurring in 2019. The purpose of this investigation was to determine the impact of fluoroquinolone breakpoint revisions on Wisconsin clinical isolates of Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa.Design: Multi-center laboratory surveillance, with testing at a single location utilizing standardized media and susceptibility testing protocols.Methods: From the Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) program, levofloxacin and ciprofloxacin minimum inhibitory concentration (MIC) values for 1911, 1521, and 1463 Wisconsin isolates of E. coli, P. mirabilis, and P. aeruginosa, respectively, were determined by broth microdilution testing. In separate data analyses, all MIC data were interpreted using CLSI breakpoints published prior to 2019, then secondarily by using CLSI breakpoints published since 2019 (which reflect lower breakpoints for both levofloxacin and ciprofloxacin resistance). Findings were further stratified by Wisconsin Department of Health Services region.Results: Up to 3.2% decreased statewide fluoroquinolone susceptibility was observed for E. coli isolates, while 5.1% and 6.3% decreases in levofloxacin susceptibility were noted for P. aeruginosa and P. mirabilis isolates, respectively, when revised breakpoints were applied. E. coli isolates from the Western region and P. mirabilis isolates from the Southeastern region demonstrated significant shifts toward decreased fluoroquinolone susceptibility upon application of revised breakpoints. Northern region P. mirabilis isolates exhibited consistently decreased fluoroquinolone susceptibility.Conclusions: Fluoroquinolone resistance has been underreported in Wisconsin as a whole, yet geographic variability continues to exist. Targeted annual surveillance is important to identify and monitor resistance trending. Compilations of SWOTARE surveillance data can be utilized to predict the impact of future CLSI interpretive breakpoint revisions in Wisconsin.


Asunto(s)
Fluoroquinolonas , Levofloxacino , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ciprofloxacina/farmacología , Escherichia coli , Fluoroquinolonas/farmacología , Humanos , Levofloxacino/farmacología , Pruebas de Sensibilidad Microbiana , Wisconsin/epidemiología
12.
Clin Med Res ; 20(4): 185-194, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36581396

RESUMEN

Objective: In 2019, the American Thoracic Society and Infectious Diseases Society of America updated clinical practice guidelines for community-acquired pneumonia (CAP). In contrast to guidelines published in 2007, macrolide monotherapy for outpatients was made a conditional recommendation based on resistance levels. Local knowledge of current antimicrobial susceptibility is needed to guide management of CAP and other bacterial respiratory pathogens. The purpose of this study was to investigate antimicrobial susceptibility profiles and trending for Wisconsin Streptococcus pneumoniae isolates.Design: Multi-center laboratory surveillance, with testing at a central location utilizing standardized susceptibility testing protocols.Methods: Data published by the Wisconsin Department of Health Services (DHS) were augmented with data from the Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) program. Data were stratified by invasive or non-invasive sources, as well as DHS region and compared to data compiled from 2006-2010.Results: Susceptibility rates for ≥ 916 invasive S. pneumoniae assessed from 2016-2020 were greater than 91% for ceftriaxone, tetracycline, and fluoroquinolone agents and were generally higher than those from 354 non-invasive isolates. Low susceptibility rates were observed for invasive isolates of penicillin (78.7%) and erythromycin (64.8%) and were even lower for non-invasive isolates (73.8% and 59.9%, respectively). This erythromycin susceptibility rate was a significant reduction from that observed in 2006-2010 (80.4; P < 0.0002). 24.8% of isolates generated an erythromycin MIC ≥ 8 µg/mL. Statewide geographic variability was noted.Conclusions: Rates of S. pneumoniae susceptibility to parenteral penicillins and cephems, and oral tetracycline and fluoroquinolone agents, remain high throughout Wisconsin. However, low oral penicillin susceptibility rates, taken together with declining macrolide susceptibility rates, should cause clinicians to consider alternative treatment options for respiratory tract infections, especially with macrolides.


Asunto(s)
Neumonía , Infecciones del Sistema Respiratorio , Humanos , Streptococcus pneumoniae , Wisconsin/epidemiología , Antibacterianos/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Penicilinas/uso terapéutico , Neumonía/tratamiento farmacológico , Eritromicina/uso terapéutico , Macrólidos/uso terapéutico , Fluoroquinolonas/uso terapéutico , Tetraciclinas/uso terapéutico
13.
J Card Surg ; 37(12): 4437-4445, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36217989

RESUMEN

BACKGROUND: Heart-lung transplantation (HLTx) is relatively uncommon, and there is a paucity of literature to suggest an age at which older recipients may be exposed to excess risk for mortality. This analysis aimed to identify a threshold of age that predicts adverse outcomes after HLTx. METHODS: The United Network of Organ Sharing registry was used to identify adult patients undergoing HLTx from 2005 to 2021. The primary outcome was 1-year mortality. Threshold regression was used to identify the threshold at which age impacts 1-year mortality. Kaplan-Meier analysis was used to model survival, and Cox proportional hazards modeling was used for risk-adjustment. RESULTS: We identified 453 patients undergoing HLTx. Threshold analysis identified that the risk for 1-year mortality was significantly elevated beyond an age of 58 years, and 47 (10.38%) patients were older than this threshold. On Kaplan-Meier analysis, 1-year survival was significantly lower in patients > 58 years compared to younger recipients (64.7% vs. 82.0%, p = .007). After risk adjustment, the hazard ratio for 1-year mortality in recipients older than 58 years was 2.27 (95% confidence interval [1.21-4.28], p = .011). CONCLUSION: A threshold for recipient age of 58 years of age may avoid excess 1-year mortality after HLTx. However, patients older than this threshold demonstrate acceptable early and midterm survival, and the majority survive to 1 year. Advanced age should be considered in patient selection for HLTx, but may not be a contraindication for candidacy particularly in the absence of other risk factors.


Asunto(s)
Trasplante de Corazón , Trasplante de Corazón-Pulmón , Adulto , Humanos , Lactante , Persona de Mediana Edad , Estudios Retrospectivos , Modelos de Riesgos Proporcionales , Factores de Riesgo , Estimación de Kaplan-Meier , Factores de Edad
14.
Arch Pharm (Weinheim) ; 355(9): e2200095, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35642311

RESUMEN

Since the discovery of the caspase-2 (Casp2)-mediated ∆tau314 cleavage product and its associated impact on tauopathies such as Alzheimer's disease, the design of selective Casp2 inhibitors has become a focus in medicinal chemistry research. In the search for new lead structures with respect to Casp2 selectivity and drug-likeness, we have taken an approach by looking more closely at the specific sites of Casp2-mediated proteolysis. Using seven selected protein cleavage sequences, we synthesized a peptide series of 53 novel molecules and studied them using in vitro pharmacology, molecular modeling, and crystallography. Regarding Casp2 selectivity, AcITV(Dab)D-CHO (23) and AcITV(Dap)D-CHO (26) demonstrated the best selectivity (1-6-fold), although these trends were only moderate. However, some analogous tetrapeptides, most notably AcDKVD-CHO (45), showed significantly increased Casp3 selectivities (>100-fold). Tetra- and tripeptides display decreased or no Casp2 affinity, supporting the assumption that a motif of five amino acids is required for efficient Casp2 inhibition. Overall, the results provide a reasonable basis for the development of both selective Casp2 and Casp3 inhibitors.


Asunto(s)
Caspasa 2 , Caspasa 2/metabolismo , Caspasa 3/metabolismo , Inhibidores de Caspasas/farmacología , Proteolisis , Relación Estructura-Actividad
15.
Opt Express ; 29(11): 15940-15952, 2021 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-34154168

RESUMEN

A cyclic atomic level scheme interacting with an optical and a microwave field is proposed for the generation and group-delay control of few-photon optical pulses. Our analysis exploits a hybrid second order-nonlinearity under conditions of electromagnetically induced transparency to generate an optical pulse. The generated pulse can be delayed or advanced through microwave intensity control of the absolute phase of the second-order-nonlinearity. Importantly, this handle on group delay of the generated pulse is number density-independent. Our scheme is thus ideally suited for the generation and control of few-photon optical pulses using ultra-dilute atomic samples. Our results will enable microscopic atomic interface systems that serve as controllable delay channels for both classical and quantum signal processing.

16.
Invest New Drugs ; 39(6): 1577-1586, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34180036

RESUMEN

The vascular endothelial growth factor (VEGF)/VEGFR and hepatocyte growth factor (HGF)/c-MET signaling pathways act synergistically to promote angiogenesis. Studies indicate VEGF inhibition leads to increased levels of phosphorylated c-MET, bypassing VEGF-mediated angiogenesis and leading to chemoresistance. We conducted a phase 1 clinical trial with 32 patients with refractory solid tumors to evaluate the safety, pharmacokinetics, and pharmacodynamics of combinations of VEGF-targeting pazopanib and the putative c-MET inhibitor ARQ197 (tivantinib) at 5 dose levels (DLs). Patients either took pazopanib and tivantinib from treatment initiation (escalation phase) or pazopanib alone for 7 days, with paired tumor sampling, prior to starting combination treatment (expansion phase). Hypertension was the most common adverse event. No more than 1 dose limiting toxicity (DLT) occurred at any DL, so the maximum tolerated dose (MTD) was not determined; DL5 (800 mg pazopanib daily and 360 mg tivantinib BID) was used during the expansion phase. Twenty of 31 evaluable patients achieved stable disease lasting up to 22 cycles. Circulating VEGF, VEGFR2, HGF, and c-MET levels were assessed, and only VEGF levels increased. Tumor c-MET levels (total and phosphorylated) were determined in paired biopsies before and after 7 days of pazopanib treatment. Total intact c-MET decreased in 6 of 7 biopsy pairs, in contrast to previously reported c-MET elevation in response to VEGF inhibition. These results are discussed in the context of our previously reported analysis of epithelial-mesenchymal transition in these tumors.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Indazoles/uso terapéutico , Neoplasias/tratamiento farmacológico , Pirimidinas/uso terapéutico , Pirrolidinonas/uso terapéutico , Quinolinas/uso terapéutico , Sulfonamidas/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Indazoles/administración & dosificación , Indazoles/efectos adversos , Indazoles/farmacocinética , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/patología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Pirimidinas/farmacocinética , Pirrolidinonas/administración & dosificación , Pirrolidinonas/efectos adversos , Pirrolidinonas/farmacocinética , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/farmacocinética , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Sulfonamidas/farmacocinética , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos
17.
Phys Chem Chem Phys ; 23(42): 24200-24210, 2021 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-34693948

RESUMEN

In this work, a series of eight similarly structured perinone chromophores were synthesized and photophysically characterized to elucidate the electronic and structural tunability of their excited state properties, including excited state redox potentials and fluorescence lifetimes/quantum yields. Despite their similar structure, these chromophores exhibited a broad range of visible absorption properties, quantum yields, and excited state lifetimes. In conjunction with static and time-resolved spectroscopies from the ultrafast to nanosecond time regimes, time-dependent computational modeling was used to correlate this behavior to the relationship between non-radiative decay and the energy-gap law. Additionally, the ground and excited state redox potentials were calculated and found to be tunable over a range of 1 V depending on the diamine or anhydride used in their synthesis (Ered* = 0.45-1.55 V; Eox* = -0.88 to -1.67 V), which is difficult to achieve with typical photoredox-active transition metal complexes. These diverse chromophores can be easily prepared, and with their range of photophysical tunability, will be valuable for future use in photofunctional applications.

18.
J Phycol ; 57(5): 1492-1503, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33960400

RESUMEN

One previously unstudied aspect of differences between sexual and asexual life stages in large-scale transport and accumulation is density (mass per unit volume) of cells in each life stage. The specific density was determined for Scrippsiella lachrymosa cells in medium with and without nitrogen (N) enrichment through density-gradient centrifugation. Growth medium without N addition is often called "encystment medium" when used for the purpose of resting cyst formation in cyst-forming dinoflagellates; mating gametes are usually seen after 2-3 days. Significant differences in specific density were found after 2 days in encystment medium simultaneously with the observation of typical gamete swimming behavior and mating. The specific density of cells in encystment medium was 1.06 g · cm-3 ; whereas, the specific density of cells in growth medium was 1.11 g · cm-3 . Cells in encystment medium were found to have significantly increased lipid content, reduced chlorophyll content, and reduced internal complexity. The findings may explain differential transport of less dense and chemotactically aggregating gametes into surface blooms in contrast to denser vegetative cells that perform daily vertical migration and do not aggregate. Passive accumulation of non-migrating gametes into layers in stagnant water also can be explained, as well as sinking of zygotes when the storage of highly dense starch increases. Resting cysts had a density of over 1.14 g · cm-3 and would sink to become part of the silt fraction of the sediment. We suggest that differences in behavior and buoyancy between sexual and asexual life stages cause differences in cell accumulation, and therefore large-scale, environmental transport could be directly dependent upon life-cycle transitions.


Asunto(s)
Dinoflagelados , Animales , Clorofila , Hidrodinámica , Estadios del Ciclo de Vida , Cigoto
19.
Clin Radiol ; 76(11): 864.e13-864.e23, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34420686

RESUMEN

Thermal ablation is a minimally invasive technique that is growing in acceptance and popularity in the management of early lung cancers. Although curative resection remains the optimal treatment strategy for stage I pulmonary malignancies, percutaneous ablative treatments may also be considered for selected patients. These techniques can additionally be used in the treatment of oligometastatic disease. Thermal ablation of early lung tumours can be achieved using several different techniques. For example, microwave ablation (MWA) and radiofrequency ablation (RFA) utilise extreme heat, whereas cryoablation uses extremely cold temperatures to cause necrosis and ultimately cell death. Typically, post-ablation imaging studies are performed within the first 1-3 months with subsequent imaging performed at regular intervals to ensure treatment response and to evaluate for signs of recurrent disease. Surveillance imaging is usually undertaken with computed tomography (CT) and integrated positron-emission tomography (PET)/CT. Typical imaging findings are usually seen on CT and PET/CT following thermal ablation of lung tumours, and it is vital that radiologists are familiar with these appearances. In addition, radiologists should be aware of the imaging findings that indicate local recurrence following ablation. The objective of this review is to provide an overview of the expected post-treatment findings on CT and PET/CT following thermal ablation of early primary lung malignancies, as well as describing the imaging appearances of local recurrence.


Asunto(s)
Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Ablación por Catéter , Humanos , Pulmón/diagnóstico por imagen , Resultado del Tratamiento
20.
J Strength Cond Res ; 35(Suppl 12): S103-S110, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31809463

RESUMEN

ABSTRACT: Jones, TW, Shillabeer, BC, Ryu, JH, and Cardinale, M. Development in adolescent middle-distance athletes: a study of training loadings, physical qualities, and competition performance. J Strength Cond Res 35(12S): S103-S110, 2021-The purpose of this study was to examine changes in running performance and physical qualities related to middle-distance performance over a training season. The study also examined relationships between training loading and changes in physical qualities as assessed by laboratory and field measures. Relationships between laboratory and field measures were also analyzed. This was a 9-month observational study of 10 highly trained adolescent middle-distance athletes. Training intensity distribution was similar over the observational period, whereas accumulated and mean distance and training time and accumulated load varied monthly. Statistically significant (p < 0.05) and large effect sizes (Cohen's d) (>0.80) were observed for improvements in: body mass (5.6%), 600-m (4.6%), 1,200-m (8.7%), and 1,800-m (6.1%) time trial performance, critical speed (7.1%), V̇o2max (5.5%), running economy (10.1%), vertical stiffness (2.6%), reactive index (3.8%), and countermovement jump power output relative to body mass (7.9%). Improvements in 1,800 m TT performance were correlated with increases in V̇o2max (r = 0.810, p = 0.015) and critical speed (r = 0.918, p = 0.001). Increases in V̇o2max and critical speed were also correlated (r = 0.895, p = 0.003). Data presented here indicate that improvements in critical speed may be reflective of changes in aerobic capacity in adolescent middle-distance athletes.


Asunto(s)
Rendimiento Atlético , Carrera , Adolescente , Atletas , Humanos , Fuerza Muscular
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