Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 799
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
J Am Chem Soc ; 145(16): 8800-8804, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37058609

RESUMO

We report a method to synthesize ultra-high-molecular-weight poly(1,3-dioxolane) (UHMW pDXL), a chemically recyclable thermoplastic material with excellent physical properties. We aimed to enhance the mechanical properties of sustainable polymers by increasing the molecular weight and found that UHMW pDXL exhibits similar tensile properties to ultra-high-molecular-weight polyethylene (UHMWPE). The new polymerization method uses metal-free and economically friendly initiators to achieve UHMW pDXL with molecular weights greater than 1000 kDa. The development of UHMW pDXL provides a potential solution for capturing value from plastic waste and addressing the detrimental effects of plastic waste.

2.
Lab Invest ; 102(4): 363-375, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34934182

RESUMO

The alveolar bone is a unique osseous tissue due to the presence of the teeth and the proximity of commensal oral microbes. Commensal microbe effects on alveolar bone homeostasis have been attributed to the oral microbiota, yet the impact of commensal gut microbes is unknown. Study purpose was to elucidate whether commensal gut microbes regulate osteoimmune mechanisms and skeletal homeostasis in alveolar bone. Male C57BL/6T germfree (GF) littermate mice were maintained as GF or monoassociated with segmented filamentous bacteria (SFB), a commensal gut bacterium. SFB has been shown to elicit broad immune response effects, including the induction of TH17/IL17A immunity, which impacts the development and homeostasis of host tissues. SFB colonized the gut, but not oral cavity, and increased IL17A levels in the ileum and serum. SFB had catabolic effects on alveolar bone and non-oral skeletal sites, which was attributed to enhanced osteoclastogenesis. The alveolar bone marrow of SFB vs. GF mice had increased dendritic cells, activated helper T-cells, TH1 cells, TH17 cells, and upregulated Tnf. Primary osteoblast cultures from SFB and GF mice were stimulated with vehicle-control, IL17A, or TNF to elucidate osteoblast-derived signaling factors contributing to the pro-osteoclastic phenotype in SFB mice. Treatment of RAW264.7 osteoclastic cells with supernatants from vehicle-stimulated SFB vs. GF osteoblasts recapitulated the osteoclast phenotype found in vivo. Supernatants from TNF-stimulated osteoblasts normalized RAW264.7 osteoclast endpoints across SFB and GF cultures, which was dependent on the induction of CXCL1 and CCL2. This report reveals that commensal gut microbes have the capacity to regulate osteoimmune processes in alveolar bone. Outcomes from this investigation challenge the current paradigm that alveolar bone health and homeostasis is strictly regulated by oral microbes.


Assuntos
Osso e Ossos , Osteoclastos , Animais , Bactérias , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/metabolismo , Células Th17
3.
FASEB J ; 35(11): e22015, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34699641

RESUMO

Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6- to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline- versus vehicle-treated germ-free mice had similar alveolar bone loss outcomes, implying that antimicrobial-driven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring alveolar bone loss in SPF mice. Chlorhexidine further disrupted the oral bacteriome and worsened alveolar bone loss in minocycline-treated SPF mice, validating that antimicrobial-induced oral dysbiosis has deleterious effects on alveolar bone. Minocycline enhanced osteoclast size and interface with alveolar bone in SPF mice. Neutrophils and plasmacytoid dendritic cells were upregulated in cervical lymph nodes of minocycline-treated SPF mice. Paralleling the upregulated proinflammatory innate immune cells, minocycline therapy increased TH 1 and TH 17 cells that have known pro-osteoclastic actions in the alveolar bone. This report reveals that antimicrobial perturbation of the commensal microbiota induces a proinflammatory oral dysbiotic state that exacerbates naturally occurring alveolar bone loss.


Assuntos
Perda do Osso Alveolar/microbiologia , Antibacterianos/efeitos adversos , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
4.
Eur J Appl Physiol ; 122(3): 591-597, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34853895

RESUMO

INTRODUCTION: Cardiovascular events are a leading cause of firefighter duty-related death, with the greatest risk occurring during or shortly after fire suppression activity. Increased cardiovascular risk potentially manifests from detrimental changes in ventricular function, vascular load, and their interaction, described as ventricular-vascular coupling. PURPOSE: To determine the effect of live-fire training on ventricular-vascular coupling. METHODS: Sixty-eight male (28 [Formula: see text] 7 years, 26.9 [Formula: see text] 3.9 kg/m2) and fifteen female (36 [Formula: see text] 8 years, 24.3 [Formula: see text] 3.9 kg/m2) firefighters completed hemodynamic and cardiac measures before and after 3 h of intermittent live-fire training. Left ventricular function was assessed as ejection fraction (EF) and ventricular elastance (ELV: end systolic pressure [ESP]/end systolic volume) via echocardiography and applanation tonometry-estimated ESP. Vascular load was assessed as arterial elastance (EA: ESP/stroke volume [SV]). Ventricular-vascular coupling (VVC) was quantified as the ratio of EA to ELV and indexed to body surface area (EAI, ELVI). RESULTS: Following firefighting EF decreased (p < 0.01) with no change in ELVI (p = 0.34). SV decreased (p < 0.01) with no change in ESP (p = 0.09), driving a significant increase in EAI (p < 0.01). These changes resulted in a significant increase in the VVC ratio (p < 0.01). CONCLUSION: The findings suggest that firefighting does not alter ventricular elastance but increases arterial elastance in healthy firefighters, resulting in a mismatch between ventricular and vascular systems. This increase in ventricular-vascular coupling ratio and concomitant reduction in ventricular systolic function may contribute to increased cardiovascular risk following live firefighting.


Assuntos
Bombeiros , Incêndios , Fatores de Risco de Doenças Cardíacas , Exposição Ocupacional/efeitos adversos , Função Ventricular Esquerda , Adulto , Determinação da Pressão Arterial , Vasos Sanguíneos/fisiopatologia , Superfície Corporal , Ecocardiografia , Feminino , Monitorização Hemodinâmica , Humanos , Masculino , Volume Sistólico
5.
Eur J Appl Physiol ; 122(10): 2189-2200, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35796827

RESUMO

Breast cancer survivors (BCS) have a high prevalence of cardiovascular disease and low cardiorespiratory fitness (CRF). CRF is an important predictor of survival in BCS. However, the physiological factors that contribute to low CRF in BCS have not been completely elucidated. To assess differences in physiological factors (cardiac, pulmonary, muscle function) related to CRF between BCS and controls. Twenty-three BCS and 23 age-body mass index (BMI) matched controls underwent a peak cycling exercise test to determine CRF, with physiological factors measured at resting and at peak exercise. Cardiac hemodynamics (stroke volume [SV], SVindex, heart rate [HR], cardiac output [Formula: see text], and [Formula: see text]index) were evaluated using ultrasonography. Pulmonary function was evaluated using the oxygen uptake efficiency slope (OUES), ventilation to carbon dioxide production slope [Formula: see text] and breathing reserve at peak exercise (BR). Muscle oxygenation variables (oxygenated [HbO2] deoxygenated [HHb] and total hemoglobin [Hb], and tissue oxygenation index [TSI]) were measured with near-infrared spectroscopy (NIRS). Both groups had similar CRF and similarly increased all hemodynamic variables (HR, SV, SVindex, [Formula: see text] and [Formula: see text]index) at peak exercise compared to resting (p < 0.001). BCS had higher overall HR and lower SVindex (group effect, p < 0.05). BCS had similar OUES, [Formula: see text] and BR compared to the controls. Both groups decreased TSI, and increased Hb and HHb similarly at peak exercise compared to resting (p < 0.001). Our data suggest BCS do not exhibit differences in cardiac, pulmonary, or muscle function at peak exercise compared to controls, when both groups have similar CRF and physical activity.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Aptidão Cardiorrespiratória , Débito Cardíaco , Teste de Esforço , Feminino , Humanos , Músculos , Consumo de Oxigênio/fisiologia
6.
Int J Behav Med ; 29(2): 240-246, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34018138

RESUMO

BACKGROUND: This report investigates the impact of a remote physical activity intervention on self-efficacy, satisfaction with functioning, and health-related quality of life (HRQOL) as assessed by the SF-36 in obese older adults with chronic pain. The intervention was group-mediated in nature and based in social cognitive theory and mindfulness-based relapse prevention. METHODS: Participants (N = 28; 70.21 ± 5.22 years) were randomly assigned to receive either the active intervention, which focused on reducing caloric intake and increasing steps across the day or to a waitlist control condition. RESULTS: Over 12 weeks, intervention participants reported a moderate, positive improvement in self-efficacy for walking relative to control. They also reported large magnitude improvements in satisfaction for physical functioning as well as improvements on pain and the physical functioning subscales of the SF-36. CONCLUSIONS: These findings expand on previous research showing similar effects in response to structured exercise, this time via a protocol that is likely to be scalable and sustainable for many older adults. Additional work on larger and more diverse samples is warranted.


Assuntos
Dor Crônica , Qualidade de Vida , Idoso , Dor Crônica/terapia , Comportamentos Relacionados com a Saúde , Humanos , Manejo da Dor , Satisfação Pessoal , Projetos Piloto , Autoeficácia
7.
Phys Rev Lett ; 127(24): 241102, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34951783

RESUMO

High-quality optical resonant cavities require low optical loss, typically on the scale of parts per million. However, unintended micron-scale contaminants on the resonator mirrors that absorb the light circulating in the cavity can deform the surface thermoelastically and thus increase losses by scattering light out of the resonant mode. The point absorber effect is a limiting factor in some high-power cavity experiments, for example, the Advanced LIGO gravitational-wave detector. In this Letter, we present a general approach to the point absorber effect from first principles and simulate its contribution to the increased scattering. The achievable circulating power in current and future gravitational-wave detectors is calculated statistically given different point absorber configurations. Our formulation is further confirmed experimentally in comparison with the scattered power in the arm cavity of Advanced LIGO measured by in situ photodiodes. The understanding presented here provides an important tool in the global effort to design future gravitational-wave detectors that support high optical power and thus reduce quantum noise.

8.
Diabet Med ; 38(4): e14407, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32961604

RESUMO

AIM: To determine whether macrovascular disease assessed by carotid ultrasonography and arterial stiffness by pulse wave velocity are independently associated with diabetic retinopathy in type 2 diabetes. METHODS: A random subgroup of surviving participants with type 2 diabetes from the Fremantle Diabetes Study Phase II were invited to take part in this sub-study in 2018-2019. In addition to standardized questionnaires, a physical examination and fasting biochemical tests, each underwent dilated colour fundus photography, carotid arterial ultrasonography with measurement of the intima-media thickness (IMT) and quantification of the degree of stenosis, and pulse wave analysis calculation of the carotid-femoral pulse wave velocity (cfPWV). The cross-sectional association between arterial disease parameters and diabetic retinopathy was assessed using generalized estimating equation models which enabled both eyes to be included in the analysis. RESULTS: Some 270 participants [mean ± sd age 72 ± 9 years, 153 (57%) men and median (IQR) diabetes duration 15 (11-22) years] were included in analysis. Of 524 assessable eyes, 82 (16%) had diabetic retinopathy. In multivariable analysis, significant independent associates of diabetic retinopathy were age at diabetes diagnosis (inversely), HbA1c , insulin treatment and urinary albumin to creatinine ratio (all P ≤ 0.022), as well as cfPWV [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03, 1.23 per 1 m/s increase; P = 0.008] and common carotid artery (CCA) IMT ≥1 mm (OR 2.95, 95% CI 1.21, 7.23; P = 0.018). CONCLUSIONS: The association between diabetic retinopathy and CCA IMT suggests that carotid disease may share cardiovascular risk factors with diabetic retinopathy. The association between diabetic retinopathy and cfPWV may reflect the consequences of altered intravascular haemodynamics.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Diabetes Mellitus Tipo 2 , Retinopatia Diabética/epidemiologia , Rigidez Vascular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/complicações , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/fisiopatologia , Retinopatia Diabética/complicações , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco , Ultrassonografia
9.
Exp Physiol ; 106(7): 1643-1653, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33938052

RESUMO

NEW FINDINGS: What is the central question of this study? Does cerebrovascular pulsatility respond differently to acute increases in arterial stiffness in middle-aged compared with young adults? What is the main finding and its importance? Compared with young adults, middle-aged adults exhibited similar changes in cerebral pulsatile damping despite attenuated changes in carotid diameter and cerebrovascular pulsatility during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness. ABSTRACT: Acute manipulation of arterial stiffness through interventions that increase sympathetic activity might provoke cerebral pulsatility and damping and reveal whether cerebrovascular haemodynamics respond differently to transient elevations in arterial stiffness in middle-aged compared with young adults. We compared cerebral pulsatility and damping in middle-aged versus young adults during two different sympathetic interventions [cold pressor test (CP) and lower-body negative pressure (LBNP)] that increase arterial stiffness acutely. Cerebrovascular haemodynamics were assessed in 15 middle-aged (54 ± 7 years old; 11 female) and 15 sex-matched young adults (25 ± 4 years old) at rest and during the CP test (4 min, 6.4 ± 0.8°C) and LBNP (6 min, -20 mmHg). Mean blood pressure was measured continuously via finger photoplethysmography. Carotid-femoral pulse wave velocity (cfPWV) and carotid stiffness were measured via tonometry and ultrasound. Blood velocity pulsatility index (PI) was measured at the middle cerebral (MCA) and common carotid artery (CCA) using Doppler, with pulsatile damping calculated as CCA PI divided by MCA PI. Increases in cfPWV were driven by changes in mean pressure during CP but not during LBNP in both groups (P < 0.05). Pulsatile damping decreased in both groups (P < 0.05) despite reductions in MCA PI and greater carotid dilatation during CP in young compared with middle-aged adults (P < 0.05). Pressure-independent increases in cfPWV during LBNP did not alter pulsatile damping but decreased MCA PI in both young and middle-aged adults (P < 0.05). These data suggest that changes in carotid diameter and cerebrovascular pulsatility differ between young and middle-aged adults despite similar changes in cerebral pulsatile damping during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness.


Assuntos
Rigidez Vascular , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Circulação Cerebrovascular/fisiologia , Feminino , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Análise de Onda de Pulso , Rigidez Vascular/fisiologia , Adulto Jovem
10.
J Am Chem Soc ; 142(47): 20161-20169, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33176426

RESUMO

Reversible-deactivation chain transfer is a viable strategy to increase the catalytic efficiency of ring-opening polymerizations, such as the alternating copolymerization of epoxides and cyclic anhydrides. In conjunction with the catalyst, protic chain transfer agents (CTAs) initiate polymerization and facilitate rapid proton transfer between active and dormant chains. Functional-group-tolerant Lewis acid catalysts are therefore required to successfully apply protic CTAs in reversible-deactivation ring-opening copolymerizations (RD-ROCOP), yet the predominant binary Lewis acid catalyst/nucleophilic cocatalyst systems suffer lower polymerization rates when used with protic CTAs. New mechanistic insight into the inhibition pathways reveals that the alcohol chain ends compete with epoxide binding to the Lewis acid and hydrogen-bond with anionic chain ends to impede epoxide ring opening. We report that a bifunctional aminocyclopropenium aluminum salen complex maintains excellent activity in the presence of protic functionality, exhibiting resilience against these inhibition pathways, even at high CTA concentrations. We apply reversible-deactivation chain transfer in the bifunctional ROCOP system to demonstrate precise molecular-weight control, CTA functional group scope, and accessible polymer architectures.

11.
Am J Phys Anthropol ; 171(4): 725-732, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31912896

RESUMO

OBJECTIVES: Previously, we found that maximum ingested bite size (Vb ), the largest piece of food an animal can consume without biting it into smaller pieces first, isometrically scales relative to body size in strepsirrhines and with negative allometry in anthropoids. In the current study, we rectify the omission of great apes from the earlier sample to now characterize the Vb of the entire size-range of the order. MATERIALS AND METHODS: Five gorillas (Gorilla gorilla gorilla-G. g. gorilla) were studied to ascertain Vb in relation to the mechanical properties of five foods. RESULTS: Gorilla Vb ranged from 166.38 cm3 (for the least obdurate food: watermelon) to 8 cm3 (for the most obdurate food: turnip), with an average Vb of 33.50 cm3 across all food types. CONCLUSIONS: When these data were compared to those from our previous studies, we found that gorillas consumed relatively slightly smaller volumes of food compared to the trend found across primates. However, because the more frugivorous gorillas consumed relatively larger pieces of food than the large folivorous monkeys previously studied, including the gorilla data increased the slope of the linear regression between body mass and Vb in anthropoids. Thus, the addition of the largest living primate brings the anthropoid Vb trend closer to the Vb trend of the order. Notwithstanding, there is still negative allometry in anthropoid Vb , in contrast with the isometry in strepsirrhine Vb . Future research should include species with body masses between the smaller anthropoids and gorillas by studying the Vb of large papionids and the other great apes.


Assuntos
Antropologia Física , Força de Mordida , Gorilla gorilla/fisiologia , Mastigação/fisiologia , Ração Animal/análise , Animais , Feminino , Masculino
12.
J Am Chem Soc ; 141(32): 12760-12769, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31380637

RESUMO

Advances in catalysis have enabled the ring-opening copolymerization of epoxides and cyclic anhydrides to afford structurally and functionally diverse polyesters with controlled molecular weights and dispersities. However, the most common systems employ binary catalyst/cocatalyst pairs which suffer from slow polymerization rates at low loadings. Inspired by new mechanistic insight into the function of binary metal salen/nucleophilic cocatalyst systems at low concentrations, we report a bifunctional complex in which the salen catalyst and an aminocyclopropenium cocatalyst are covalently tethered. A modular ligand design circumvents the extended linear syntheses typical of bifunctional catalysts, enabling systematic variation to understand and enhance catalytic activity. The optimized bifunctional aluminum salen catalyst maintains excellent activity for the ring-opening copolymerization of epoxides and cyclic anhydrides at low concentrations (≥0.025 mol %), and the aminocyclopropenium cocatalyst suppresses undesirable transesterification and epimerization side reactions, preserving the integrity of the polymer backbone.

13.
J Am Chem Soc ; 141(25): 10060-10067, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31244138

RESUMO

Mechanochromic functionality realized through force-responsive molecules (i.e., mechanophores) has great potential for spatially localized damage warning in polymers. However, in structural plastics, for which damage warning is most critical, this approach has had minimal success because brittle failure typically precedes detectable color change. Herein, we report on the room-temperature mechanochromic activation of spiropyran in high Tg bisphenol A polycarbonate. The mechanochromic functionality was introduced by polymerization of dihydroxyspiropyran as a comonomer while retaining the excellent thermomechanical properties of the polycarbonate. The mechanochromic behavior is thoroughly evaluated in response to changes in stress, deformation, and time, providing new insights regarding how loading history controls stress accumulation in polymer chains. In addition, a new method to incorporate mechanochromic functionality in structures without dispersing costly mechanophores in the bulk is demonstrated by using a mechanochromic laminate. The room-temperature mechanochromic activation in a structural polymer combined with the new and efficient preparation and processing methods bring us closer to the application of mechanochromic smart materials.

14.
J Appl Microbiol ; 125(2): 383-397, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29624820

RESUMO

AIM: To understand the underlying cellular mechanisms during inactivation of Escherichia coli in response to antimicrobial solution of nonthermal plasma-activated N-acetylcysteine (NAC). METHODS AND RESULTS: The recommended techniques were used to demonstrate E. coli cellular and transcriptomic changes caused associated with peroxynitrite and compared with plasma-treated NAC solution. The findings demonstrate that E. coli cells respond to plasma-treated NAC and undergo severe oxidative and nitrosative stress, and leading to stress-induced damages to different components of bacterial cells, which includes loss of membrane potential, formation of oxidized glutathione (GSSG), formation of nitrotyrosine (a known marker of nitrosative stress), DNA damage, and generated a prominent pool of peroxynitrite. Reverse-transcriptase (RT)-polymerase chain reaction analysis of reactive nitrogen species (RNS) responsive genes indicated their differential expressions. CONCLUSION: For the first time, we report that the plasma-treated NAC solution activates predominantly nitrosative stress-responsive genes in E. coli and is responsible for cell death. SIGNIFICANCE AND IMPACT OF THE STUDY: The reactive species generated in solutions by nonthermal plasma treatment depends on the type of solution or solvent used. The plasma-treated NAC solution rapidly inactivates E. coli, mostly involving highly RNS generated in NAC solution, and has high potential as disinfectant.


Assuntos
Acetilcisteína/farmacologia , Escherichia coli/efeitos dos fármacos , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Plasma , Dano ao DNA/efeitos dos fármacos , Escherichia coli/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Ácido Peroxinitroso/metabolismo
15.
Ann Plast Surg ; 80(6S Suppl 6): S410-S417, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29746273

RESUMO

BACKGROUND: Biomedical devices are implanted into mammalian soft tissues to improve, monitor, or restore form or function. The utility of these implants is limited by the subsequent foreign body response (FBR), beginning with inflammation and terminating in a collagen envelope around the device, known as the capsule. This capsule then can contract and distort the shape of the device or limit its effectiveness in interacting with the surrounding host tissues. In the current study, we investigated the effect of therapeutic collagen-coated silicone discs in a rat model of the FBR. METHODS: A 3-dimensional printed mold was used to fabricate collagen-coated silicone discs incorporating 3 therapeutic agents: colchicine, a function-blocking antibody against interleukin 8 (IL-8) receptor B, and a powerful anti-inflammatory steroid, dexamethasone. Discs were implanted submuscularly into a well-characterized rat model of the FBR and evaluated for inflammatory response, fibrotic development, and cytokine release. RESULTS: Coated silicone discs exhibited reduced collagen deposition and little to no foreign body giant cells at the host-silicone interface when compared with the silicone-only group. Therapeutic hydrogels demonstrate a significant decrease in cellular infiltration into the coatings over the 2-week time point in contrast to therapeutic-free hydrogel coatings. Cytokine analysis revealed significant differences between therapeutic-free and therapeutic-containing coatings when compared with silicone-only controls. Levels of IL-1ß, IL-6, monocyte chemotactic protein 1, and macrophage inflammatory protein 3α were affected 48 hours after implantation, while differences in IL-18, growth-regulated oncogene/keratinocyte chemoattractant, and macrophage inflammatory protein 3α were observed 1 week after implantation. CONCLUSIONS: By utilizing the host's innate immune response, our engineered hydrogel coatings delivered therapeutic moieties directly to the implant microenvironment, thus delaying the FBR up to 2 weeks.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colágeno/uso terapêutico , Reação a Corpo Estranho/prevenção & controle , Hidrogéis/uso terapêutico , Próteses e Implantes/efeitos adversos , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Reação a Corpo Estranho/diagnóstico , Reação a Corpo Estranho/imunologia , Reação a Corpo Estranho/patologia , Ratos , Ratos Sprague-Dawley , Silicones/efeitos adversos , Resultado do Tratamento
16.
Pediatr Surg Int ; 34(2): 227-235, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29022081

RESUMO

PURPOSE: To review demographics, effect of preoperative chemotherapy on tumour thrombus, imaging, operative strategy, and outcomes of 12 patients presenting with intracardiac extension of Wilms tumour thrombus. METHODS: A retrospective audit was undertaken on patients with intracardiac extension of Wilms tumour. Patients were identified from the oncology database and information obtained on clinical presentation, stage, preoperative treatment, surgical procedures and complications, histology, and survival status. Ethics approval was obtained from the University of Cape Town Human Research Ethics Committee. RESULTS: From 1984 to 2016, 337 children with Wilms tumour were treated. Twelve (3.6%) had intracardiac extension of tumour thrombus, nine into the right atrium, and three into the right ventricle. Ultrasound, computerized tomography, magnetic resonance imaging, and echocardiograms were used to assess thrombus level. Patients were staged as stage III(8) and IV(4). All patients received preoperative chemotherapy. Thrombus retracted from the heart in two cases. One patient died preoperatively. Eleven underwent laparotomy, median sternotomy, and cardiopulmonary bypass (CPB). Four underwent cavectomy. Five required cavoatrial patches. Thrombus extending into the hepatic veins was extracted in five patients. There was one intraoperative complication and one perioperative death. Thrombus histology showed viable tumour in 9 of 11 patients. Three patients died of progressive disease. Seven patients are currently disease free. CONCLUSION: A combination of imaging is required to determine thrombus extent, and this facilitates surgical planning. Preoperative chemotherapy may cause thrombus regression, thus avoiding CPB. CPB offers appropriate conditions for safe tumour thrombus excision. Full management in centres with appropriately experienced staff and facilities for CPB is recommended.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias/etiologia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Trombose/etiologia , Tumor de Wilms/cirurgia , Criança , Pré-Escolar , Feminino , Átrios do Coração , Cardiopatias/diagnóstico , Cardiopatias/cirurgia , Ventrículos do Coração , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico , Masculino , Estudos Retrospectivos , Trombose/diagnóstico , Trombose/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tumor de Wilms/complicações , Tumor de Wilms/patologia
17.
J Environ Manage ; 210: 338-348, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29367142

RESUMO

Closing of the marine commons increases economic returns and slows depletion of valuable ocean resources. Rights-based management is widely used for fisheries rationalization. Regulators with sound biological and economic information can in theory set overall harvest control rules that protect the fish stocks, and manage for external costs and benefits from harvest. These may include ecosystem damages, overcapitalization in the fishery, and/or equity concerns. Regulatory efforts and related rights-based management instruments may increase the returns to fishery stakeholders but miss important challenges that are increasing under climate change. These include transboundary resource management and tradeoffs between local economic returns and Total Economic Value. The case of the valuable, yet invasive, crab species, Chionoecetes Opilio (Snow Crab) in the Barents Sea illustrates the concerns. The spread of the crab has known and unknown ecosystem and commercial fishery risks, particularly to uncertain ecosystem values. We show how the progression of the biological invasion interacts with human strategic behavior to identify limitations of management options. Open access harvesting of the species in international waters has generated a positive spillover effect by slowing the westward spread of the species to sensitive benthic ecosystems. This benefit is threatened by reclassification of the crab as a "sedentary species" (one which is not capable of leaving the seabed when harvestable (UNCLOS, 1982, article 77, part VI)). This shifts the regulatory environment for the crab in ways that exacerbate the invasion in exchange for protection of local gains. Such problems will increase in magnitude and impact as climate changes increasingly affect species' ranges. Optimal decision-making regarding profitable species in new ecosystems must incorporate how strategic institutional shifts occurring in response to the economic incentives asymmetrically affect local and global stakeholders in addition to standard concerns over ecological and economic damages.


Assuntos
Braquiúros , Conservação dos Recursos Naturais , Ecossistema , Animais , Pesqueiros , Atividades Humanas , Humanos
18.
Phys Rev Lett ; 118(15): 151102, 2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28452534

RESUMO

Interferometric gravitational wave detectors operate with high optical power in their arms in order to achieve high shot-noise limited strain sensitivity. A significant limitation to increasing the optical power is the phenomenon of three-mode parametric instabilities, in which the laser field in the arm cavities is scattered into higher-order optical modes by acoustic modes of the cavity mirrors. The optical modes can further drive the acoustic modes via radiation pressure, potentially producing an exponential buildup. One proposed technique to stabilize parametric instability is active damping of acoustic modes. We report here the first demonstration of damping a parametrically unstable mode using active feedback forces on the cavity mirror. A 15 538 Hz mode that grew exponentially with a time constant of 182 sec was damped using electrostatic actuation, with a resulting decay time constant of 23 sec. An average control force of 0.03 nN was required to maintain the acoustic mode at its minimum amplitude.

19.
Mol Psychiatry ; 21(3): 339-47, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26008736

RESUMO

The search for genetic variants underlying major depressive disorder (MDD) has not yet provided firm leads to its underlying molecular biology. A complementary approach is to study gene expression in relation to MDD. We measured gene expression in peripheral blood from 1848 subjects from The Netherlands Study of Depression and Anxiety. Subjects were divided into current MDD (N=882), remitted MDD (N=635) and control (N=331) groups. MDD status and gene expression were measured again 2 years later in 414 subjects. The strongest gene expression differences were between the current MDD and control groups (129 genes at false-discovery rate, FDR<0.1). Gene expression differences across MDD status were largely unrelated to antidepressant use, inflammatory status and blood cell counts. Genes associated with MDD were enriched for interleukin-6 (IL-6)-signaling and natural killer (NK) cell pathways. We identified 13 gene expression clusters with specific clusters enriched for genes involved in NK cell activation (downregulated in current MDD, FDR=5.8 × 10(-5)) and IL-6 pathways (upregulated in current MDD, FDR=3.2 × 10(-3)). Longitudinal analyses largely confirmed results observed in the cross-sectional data. Comparisons of gene expression results to the Psychiatric Genomics Consortium (PGC) MDD genome-wide association study results revealed overlap with DVL3. In conclusion, multiple gene expression associations with MDD were identified and suggest a measurable impact of current MDD state on gene expression. Identified genes and gene clusters are enriched with immune pathways previously associated with the etiology of MDD, in line with the immune suppression and immune activation hypothesis of MDD.


Assuntos
Transtornos de Ansiedade/genética , Transtorno Depressivo Maior/genética , Expressão Gênica/genética , Predisposição Genética para Doença/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos Transversais , Transtorno Depressivo Maior/diagnóstico , Feminino , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla , Humanos , Interleucina-6/metabolismo , Células Matadoras Naturais/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/genética
20.
Biomacromolecules ; 18(10): 3359-3366, 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-28893064

RESUMO

GM1 ganglioside is known to promote amyloid-ß (Aß) peptide aggregation in Alzheimer's disease. The roles of the individual saccharides and their distribution in this process are not understood. Acrylamide-based glycomonomers with either ß-d-glucose or ß-d-galactose pendant groups were synthesized to mimic the stereochemistry of saccharides present in GM1 and characterized via 1H NMR and electrospray ionization mass spectrometry. Glycopolymers of different molecular weights were synthesized by aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization and characterized by NMR and GPC. The polymers were used as models to investigate the effects of molecular weight and saccharide unit type on Aß aggregation via thioflavin-T fluorescence and PAGE. High molecular weight (∼350 DP) glucose-containing glycopolymers had a profound effect on Aß aggregation, promoting formation of soluble oligomers of Aß and limiting fibril production, while the other glycopolymers and negative control had little effect on the Aß propagation process.


Assuntos
Acrilamida/química , Peptídeos beta-Amiloides/química , Materiais Biomiméticos/síntese química , Gangliosídeo G(M1)/química , Galactose/análogos & derivados , Glucose/análogos & derivados , Benzotiazóis , Materiais Biomiméticos/química , Polimerização , Agregados Proteicos , Tiazóis/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA