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The current urogynecological clinical meshes trigger unfavorable foreign body response which leads to graft failure in the long term. To overcome the present challenge, we applied a tissue engineering strategy using endometrial SUSD2+ mesenchymal stem cells (eMSCs) with high regenerative properties. This study delves deeper into foreign body response to SUSD2+ eMSC based degradable PLACL/gelatin nanofiber meshes using a mouse model targeted at understanding immunomodulation and mesh integration in the long term. Delivery of cells with nanofiber mesh provides a unique topography that enables entrapment of therapeutic cells for up to 6 weeks that promotes substantial cellular infiltration of host anti-inflammatory macrophages. As a result, degradation rate and tissue integration are highly impacted by eMSCs, revealing an unexpected level of implant integration over 6 weeks in vivo. From a clinical perspective, such immunomodulation may aid in overcoming the current challenges and provide an alternative to an unmet women's urogynecological health need.
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Endométrio/citologia , Procedimentos Cirúrgicos em Ginecologia/instrumentação , Células-Tronco Mesenquimais/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Implantes Absorvíveis/efeitos adversos , Animais , Anti-Inflamatórios/química , Células Cultivadas , Feminino , Gelatina/química , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Poliésteres/química , Telas Cirúrgicas/efeitos adversos , Alicerces Teciduais/efeitos adversosRESUMO
The rapid formation of hydrazones under physiological conditions was exploited for the detection of aldehydes through chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI). A metal-free, diamagnetic contrast agent derived from N-amino anthranilic acid was introduced, which selectively "turned-on" upon hydrazone formation through an effect termed Hydrazo-CEST. While the hydrazine form of the probe produced no CEST-MRI signal enhancement, the formation of the aryl hydrazone resulted in >20 % intensity decrease in the bulk water signal through the CEST effect, as measured by 300â MHz 1 Hâ NMR, 3â T and 7â T MRI. Both the electronic contributions of the N-amino anthranilate and the aldehyde binding partner were shown to directly impact the exchange rate of the proton on the ring-proximal nitrogen, and thus the imaging signal. Additionally, the presence of the carboxylic acid moiety ortho to the hydrazine was necessary not only for contrast production, but also for rapid hydrazone formation and prolonged hydrazone product stability under physiological conditions. This work provided the first example of an MRI-based contrast agent capable of a "turn on" response upon reaction with bioactive aldehydes, and outlined both the structural and electronic requirements to expand on Hydrazo-CEST, a novel, hydrazone-dependent subtype of diamagnetic CEST-MRI.
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BACKGROUND: Medications that taste unpleasant can be a struggle to administer to children, most often resulting in low adherence rates. Pictograms can be useful tools to improve adherence by conveying information to patients in a way that they will understand. METHODS: One-on-one structured interviews were conducted with parents/guardians and with children between the ages of 9 and 17 years at a pediatric hospital. The questionnaire evaluated the comprehension of 12 pictogram sets that described how to mask the taste of medications for children. Pictograms understood by >85% of participants were considered validated. Short-term recall was assessed by asking participants to recall the meaning of each pictogram set. RESULTS: There were 51 participants in the study-26 (51%) were children aged 9 to 17 years and 25 (49%) were parents or guardians. Most children (54%) had health literacy levels of grade 10 or higher. Most parents and guardians (92%) had at least a high school health literacy level. Six of the 12 pictogram sets (50%) were validated. Eleven of 12 pictogram sets (92%) had a median translucency score greater than 5. All 12 pictogram sets (100%) were correctly identified at short-term recall and were therefore validated. CONCLUSION: The addition of validated illustrations to pharmaceutical labels can be useful to instruct on how to mask the taste of medication in certain populations. Further studies are needed to assess the clinical impact of providing illustrated information to populations with low health literacy.
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OBJECTIVE: We aimed to examine whether women who adhered to Institute of Medicine (IOM) guidelines for gestational weight gain (GWG) had improved perinatal outcomes. STUDY DESIGN: This is a population-based retrospective cohort study of nulliparous women with term singleton vertex births in the United States from 2011 through 2012. Women with medical or obstetric complications were excluded. Prepregnancy body mass index was calculated using reported weight and height. Women were categorized into 4 groups based on GWG and prepregnancy body mass index: (1) weight gain less than, (2) weight gain within, (3) weight gain 1-19 lb in excess of, and (4) weight gain ≥20 lb in excess of the IOM guidelines. The χ(2) test and multivariable logistic regression analysis were used for statistical comparisons. RESULTS: Compared to women who had GWG within the IOM guidelines, women with excessive weight gain, particularly ≥20 lb, were more likely to have adverse maternal outcomes (preeclampsia: adjusted odds ratio [aOR], 2.78; 95% confidence interval [CI], 2.82-2.93; eclampsia: aOR, 2.51; 95% CI, 2.27-2.78; cesarean: aOR, 2.1; 95% CI, 2.14-2.19), blood transfusion (aOR, 1.22; 95% CI, 1.11-1.33), and neonatal outcomes (5-minute Apgar <4: aOR, 1.22; 95% CI, 1.14-1.31; ventilation use >6 hours: aOR, 1.24; 95% CI, 1.15-1.33; seizure: aOR, 1.53; 95% CI, 1.24-1.89). Women who gained less than IOM guidelines had lower risks of hypertensive disorders of pregnancy and obstetric interventions but were more likely to have small-for-gestational-age neonates (aOR, 1.55; 95% CI, 1.52-1.59). CONCLUSION: Women whose GWG is in excess of IOM guidelines have higher risk of adverse maternal and neonatal outcomes, particularly in women with ≥20 lb excess weight gain above guidelines while women who had weight gain below the IOM guidelines were less likely to have maternal morbidity but had higher odds of small for gestational age.
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Doenças do Recém-Nascido/etiologia , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Complicações na Gravidez/etiologia , Aumento de Peso , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Análise Multivariada , Guias de Prática Clínica como Assunto , Gravidez , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
Physiologically relevant in vitro models of the human outer retina are required to better elucidate the complex interplay of retinal tissue layers and investigate their role in retinal degenerative disorders. Materials currently used to mimic the function of Bruch's membrane fail to replicate a range of important structural, mechanical, and biochemical properties. Here, we detail the fabrication of a surface-functionalized, fibrous collagen I membrane. We demonstrate its ability to better replicate a range of important material properties akin to the function of human Bruch's membrane when compared with a commonly utilized synthetic polyethylene terephthalate alternative. We further reveal the ability of this membrane to support the culture of the ARPE-19 cell line, as well as human pluripotent stem cell-derived RPE-like cells and human umbilical vein endothelial cells. This material could provide greater physiological relevance to the native Bruch's membrane than current synthetic materials and further improve the outcomes of in vitro outer retinal models.
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As scientists discovered that raw neurological signals could translate into bioelectric information, brain-machine interfaces (BMI) for experimental and clinical studies have experienced massive growth. Developing suitable materials for bioelectronic devices to be used for real-time recording and data digitalizing has three important necessitates which should be covered. Biocompatibility, electrical conductivity, and having mechanical properties similar to soft brain tissue to decrease mechanical mismatch should be adopted for all materials. In this review, inorganic nanoparticles and intrinsically conducting polymers are discussed to impart electrical conductivity to systems, where soft materials such as hydrogels can offer reliable mechanical properties and a biocompatible substrate. Interpenetrating hydrogel networks offer more mechanical stability and provide a path for incorporating polymers with desired properties into one strong network. Promising fabrication methods, like electrospinning and additive manufacturing, allow scientists to customize designs for each application and reach the maximum potential for the system. In the near future, it is desired to fabricate biohybrid conducting polymer-based interfaces loaded with cells, giving the opportunity for simultaneous stimulation and regeneration. Developing multi-modal BMIs, Using artificial intelligence and machine learning to design advanced materials are among the future goals for this field. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.
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Interfaces Cérebro-Computador , Nanoestruturas , Polímeros/química , Inteligência Artificial , Hidrogéis/químicaRESUMO
Pelvic Organ Prolapse (POP) is a common gynaecological disorder where pelvic organs protrude into the vagina. While transvaginal mesh surgery using non-degradable polymers was a commonly accepted treatment for POP, it has been associated with high rates of adverse events such as mesh erosion, exposure and inflammation due to serious foreign body response and therefore banned from clinical use after regulatory mandates. This study proposes a tissue engineering strategy using uterine endometrium-derived mesenchymal stem/stromal cells (eMSC) delivered with degradable poly L-lactic acid-co-poly ε-caprolactone (PLACL) and gelatin (G) in form of a composite electrospun nanofibrous mesh (P + G nanomesh) and evaluates the immunomodulatory mechanism at the material interfaces. The study highlights the critical acute and chronic inflammatory markers along with remodelling factors that determine the mesh surgery outcome. We hypothesise that such a bioengineered construct enhances mesh integration and mitigates the Foreign Body Response (FBR) at the host interface associated with mesh complications. Our results show that eMSC-based nanomesh significantly increased 7 genes associated with ECM synthesis and cell adhesion including, Itgb1, Itgb2, Vcam1, Cd44, Cdh2, Tgfb1, Tgfbr1, 6 genes related to angiogenesis including Ang1, Ang2, Vegfa, Pdgfa, Serpin1, Cxcl12, and 5 genes associated with collagen remodelling Col1a1, Col3a1, Col6a1, Col6a2, Col4a5 at six weeks post-implantation. Our findings suggest that cell-based tissue-engineered constructs potentially mitigate the FBR response elicited by biomaterial implants. From a clinical perspective, this construct provides an alternative to current inadequacies in surgical outcomes by modulating the immune response, inducing angiogenesis and ECM synthesis during the acute and chronic phases of the FBR.
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Corpos Estranhos , Células-Tronco Mesenquimais , Nanofibras , Feminino , Camundongos , Animais , Gelatina , Engenharia Tecidual/métodos , Diafragma da Pelve , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismo , Corpos Estranhos/metabolismo , RegeneraçãoRESUMO
Neurovascular abnormalities in mouse models of 16p11.2 deletion autism syndrome are reminiscent of alterations reported in murine models of glucose transporter deficiency, including reduced brain angiogenesis and behavioral alterations. Yet, whether cerebrovascular alterations in 16p11.2df/+ mice affect brain metabolism is unknown. Here, we report that anesthetized 16p11.2df/+ mice display elevated brain glucose uptake, a phenomenon recapitulated in mice with endothelial-specific 16p11.2 haplodeficiency. Awake 16p11.2df/+ mice display attenuated relative fluctuations of extracellular brain glucose following systemic glucose administration. Targeted metabolomics on cerebral cortex extracts reveals enhanced metabolic responses to systemic glucose in 16p11.2df/+ mice that also display reduced mitochondria number in brain endothelial cells. This is not associated with changes in mitochondria fusion or fission proteins, but 16p11.2df/+ brain endothelial cells lack the splice variant NT-PGC-1α, suggesting defective mitochondrial biogenesis. We propose that altered brain metabolism in 16p11.2df/+ mice is compensatory to endothelial dysfunction, shedding light on previously unknown adaptative responses.
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Células Endoteliais , Haploinsuficiência , Camundongos , Animais , Células Endoteliais/metabolismo , Biogênese de Organelas , Deleção Cromossômica , EncéfaloRESUMO
BACKGROUND: Allergic conjunctivitis is characterized by itchy, watery and swollen eyes which occur in response to exposure to seasonal or environmental allergens. The early phase reaction of allergic conjunctivitis is primarily mediated by mast cell degranulation while the late phase reaction is driven by Th2 cells and eosinophils. Prostaglandin D(2) (PGD(2)), released from mast cells, is present in allergic conjunctival tears and may elicit classical allergic responses via interaction with the high-affinity DP2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells, CRTh2). Furthermore, antagonism of this receptor is well known to inhibit eosinophil chemotaxis, basophil activation and Th2 cytokine production. PGD(2), therefore, may be involved in both early and late phase reactions in response to allergen challenge. METHODS: Thus, we explored whether our novel and selective DP2 antagonist AM156 would be efficacious in animal models of allergic conjunctivitis. Furthermore, as respiratory syncytial virus (RSV) has been implicated in the pathogenesis of allergic conjunctivitis, we examined the effects of DP2 antagonism in a murine model of RSV ocular infection. RESULTS: Utilizing a guinea pig ovalbumin model and a murine ragweed model we demonstrated that AM156 reduces redness, discharge and swelling in response to allergen challenge. These effects were equal to or greater than those of current clinical treatment options for allergic conjunctivitis including topical corticosteroids and a dual-mechanism antihistamine and decongestant. AM156 significantly reduced RSV-induced ocular inflammation and IL-4 production. CONCLUSION: These results suggest that a topical DP2 antagonist such as AM156 may represent a novel therapeutic for allergic conjunctivitis.
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Antialérgicos/uso terapêutico , Benzilaminas/uso terapêutico , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Viral/tratamento farmacológico , Receptores Imunológicos/antagonistas & inibidores , Receptores de Prostaglandina/antagonistas & inibidores , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Administração Tópica , Alérgenos/imunologia , Ambrosia/imunologia , Animais , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/metabolismo , Conjuntivite Viral/imunologia , Conjuntivite Viral/metabolismo , Modelos Animais de Doenças , Feminino , Cobaias , Interleucina-4/imunologia , Interleucina-4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Receptores Imunológicos/imunologia , Receptores de Prostaglandina/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/metabolismoRESUMO
We report the fabrication of bio-based thermoplastic polyurethane (TPU) fibrous scaffolds containing essential oils (EO). The main goal of this study was to investigate the effects of essential oil type (St. John's Wort oil (SJWO), lavender oil (LO), and virgin olive oil (OO))/concentration on the electrospinnability of TPU. The effects of applied voltage, flow rate, and end-tip distance on the diameter, morphology, and wettability of the TPU/EO electrospun fibers were investigated. The electrospun TPU/EO scaffolds were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle (CA), and Fourier transform infrared spectroscopy (FTIR). The addition of oil resulted in an increase in the fiber diameter, reduction in the surface roughness, and, accordingly, a reduction in the contact angle of the composite fibers. TPU fibers containing SJWO and LO have a more flexible structure compared to the fibers containing OO. This comparative study fills the existing information gap and shows the benefits of the fabrication of essential-oil-incorporated electrospun fiber with morphology and size range with respect to the desired applications, which are mostly wound dressing and food packaging.
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Passive collection is an emerging sampling method for environmental DNA (eDNA) in aquatic systems. Passive eDNA collection is inexpensive and efficient, and requires minimal equipment, making it suited to high-density sampling and remote deployment. Here, we compare the effectiveness of nine membrane materials for passively collecting fish eDNA from a 3-million-litre marine mesocosm. We submerged materials (cellulose, cellulose with 1% and 3% chitosan, cellulose overlayed with electrospun nanofibres and 1% chitosan, cotton fibres, hemp fibres, and sponge with either zeolite or active carbon) for intervals between 5 and 1080 min. We show that for most materials, with as little as 5 min of submersion, mitochondrial fish eDNA measured with qPCR, and fish species richness measured with metabarcoding, was comparable to that collected by conventional filtering. Furthermore, PCR template DNA concentrations and species richness were generally not improved significantly by longer submersion. Species richness detected for all materials ranged between 11 and 37 species, with a median of 27, which was comparable to the range for filtered eDNA (19-32). Using scanning electron microscopy, we visualized biological matter adhering to the surface of materials, rather than entrapped, with images also revealing a diversity in size and structure of putative eDNA particles. eDNA can be collected rapidly from seawater with a passive approach and using a variety of materials. This will suit cost- and time-sensitive biological surveys, and where access to equipment is limited.
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Quitosana , DNA Ambiental , Animais , Biodiversidade , Celulose , Código de Barras de DNA Taxonômico/métodos , Monitoramento Ambiental/métodos , Peixes/genéticaRESUMO
Air pollution is a universal concern. The suspended solid/liquid particles in the air and volatile organic compounds (VOCs) are ubiquitous. Synthetic polymer-based air filter media not only has disposal issues but also is a source of air and water pollution at the end of their life cycle. It has been a challenge to filter both particulate matter and VOC pollutants by a common biodegradable filter media having low air resistance. This study reports gelatin/ß-cyclodextrin composite nanofiber mats with dual function air filtration ability at reduced air resistance (148 Pa) and low basis weight (1 g/m²). Gelatin/ß-cyclodextrin nanofibers captured aerosols (0.3-5 µm) with < 95% filtration efficiency at 0.029/Pa quality factor. They adsorbed great amount of xylene (287 mg/g), benzene (242 mg/g), and formaldehyde (0.75 mg/g) VOCs. VOC adsorption of gelatin/ß-cyclodextrin nanofibers is found several times higher than a commercial face mask and pristine powder samples. This study provides a solution for a 'green' dual function respiratory air filtration at low resistance. Gelatin/ß-cyclodextrin nanofibers also have the potential to filter nano-sized viruses.
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Poluentes Atmosféricos , Nanofibras , Compostos Orgânicos Voláteis , beta-Ciclodextrinas , Aerossóis , Poluentes Atmosféricos/análise , Filtração , Gelatina , Compostos Orgânicos Voláteis/análiseRESUMO
A novel dissolution method that allows for the total solvation of high-concentration, high-molecular-weight polyaniline (PANi) doped with (+)-camphor-10-sulfonic acid (CSA) is reported. Preparation of 12-16 wt % 65,000 Da PANi solutions in N,N-dimethylformamide is achievable using a simple one-pot method. Doped polyaniline solutions in common organic solvents were processed into nanofibers using a convenient single-nozzle electrospinning technique. The electrospinning of PANi-CSA into nanofibrous membranes generated substrates that were subsequently employed in colorimetric gas sensing. These substrates demonstrated linearity of response upon exposure to 50-5500 ppm ammonia at ambient (50 ± 10% RH) and high (80% RH) humidity.
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PURPOSE: To describe the multidisciplinary approaches to placenta accreta spectrum (PAS) across five tertiary care centers that comprise the University of California fetal Consortium (UCfC) and to identify potential best practices. MATERIALS AND METHODS: Retrospective review of all cases of pathologically confirmed invasive placenta delivered from 2009 to 2014 at UCfC. Differences in intraoperative management and outcomes based on prenatal suspicion were compared. Interventions assessed included ureteral stent use, intravascular balloon use, anesthetic type, gynecologic oncology (Gyn Onc) involvement, and cell saver use. Intervention variation by institution was also assessed. Analyses were adjusted for final pathologic diagnosis. Chi-square, Fisher's exact, Student's t-test, and Mann-Whitney's U-test were used as appropriate. Binary logistic regression and multivariable linear regression were used to adjust for confounders. RESULTS: One hundred and fifty-one cases of pathologically confirmed invasive placenta were identified, of which 82% (123) were suspected prenatally. There was no correlation between the degree of invasion on prenatal imaging and use of each intervention. Ureteral stents were placed in 33% (41) of cases and did not reduce GU injury. Intravascular balloons were placed in 29% (36) of cases and were associated with shorter OR time (161 versus 236 min, p < .01) and lower estimated blood loss (EBL) (1800 versus 2500 ml, p < .01). General endotracheal anesthesia (GETA) was used in 70% (86). EBL did not differ between GETA and regional anesthesia. Gyn Onc was involved in 58% (71) of cases and EBL adjusted for final pathology was reduced with their involvement (2200 versus 2250 ml, p = .02) while OR time and intraoperative complications did not differ. Cell saver was used in 20% (24) and was associated with longer OR time (296 versus 200 min, p < .01). Use of cell saver was not associated with a difference in EBL or number of units of packed red cells transfused. All analyses were adjusted for pathologic severity of invasion. CONCLUSIONS: Intravascular interventions such as uterine artery balloons and the inclusion of Gynecologic Oncologists as part of a multidisciplinary approach to treating PAS reduce EBL. Additionally, the placement of intravascular balloons may reduce OR time. No significant differences were seen in outcomes when comparing the use of ureteral stents, general anesthesia, or institutions. A team of experienced operators with a standard approach may be more significant than specific practices.
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Placenta Acreta , Feminino , Humanos , Histerectomia , Equipe de Assistência ao Paciente , Placenta Acreta/cirurgia , Gravidez , Cuidado Pré-Natal , Estudos RetrospectivosRESUMO
Prostaglandin D(2) (PGD(2)) is one of a family of biologically active lipids derived from arachidonic acid via the action of COX-1 and COX-2. PGD(2) is released from mast cells and binds primarily to two G protein-coupled receptors, namely DP1 and DP2, the latter also known as chemoattractant receptor-homologous molecule expressed on Th2 cells. DP2 is predominantly expressed on eosinophils, Th2 cells, and basophils, but it is also expressed to a lesser extent on monocytes, mast cells, and epithelial cells. Interaction of PGD(2) and its active metabolites with DP2 results in cellular chemotaxis, degranulation, up-regulation of adhesion molecules, and cytokine production. Chronic obstructive pulmonary disease (COPD) is a chronic progressive inflammatory disease characterized by elevated lung neutrophils, macrophages, and CD8+ T lymphocytes and mucus hypersecretion. Cigarette smoke contributes to the etiology of COPD and was used here as a provoking agent in a murine model of COPD. In an acute model, {2'-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4'-trifluoro-methyl-biphenyl-3-yl}-acetic acid, sodium salt (AM156) and (5-{2-[(benzoyloxycarbonyl-ethyl-amino)-methyl]-4-trifluoromethyl-phenyl}-pyridin-3-yl)-acetic acid, sodium salt) (AM206), potent DP2 receptor antagonists, dose-dependently inhibited influx of neutrophils and lymphocytes to smoke-exposed airways. In a subchronic model, AM156 and AM206 inhibited neutrophil and lymphocyte trafficking to the airways. Furthermore, AM156 and AM206 treatment inhibited mucus cell metaplasia and prevented the thickening of the airway epithelial layer induced by cigarette smoke. These data suggest that DP2 receptor antagonism may represent a novel therapy for COPD or other conditions characterized by neutrophil influx, mucus hypersecretion, and airway remodeling.
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Pulmão/efeitos dos fármacos , Muco/metabolismo , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Receptores Imunológicos/antagonistas & inibidores , Receptores de Prostaglandina/antagonistas & inibidores , Mucosa Respiratória/efeitos dos fármacos , Fumar/efeitos adversos , Animais , Benzilaminas/farmacocinética , Benzilaminas/farmacologia , Linhagem Celular , Movimento Celular , Feminino , Cobaias , Humanos , Técnicas In Vitro , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Pulmão/imunologia , Pulmão/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Metaplasia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Niacina/análogos & derivados , Niacina/farmacocinética , Niacina/farmacologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Mucosa Respiratória/patologiaRESUMO
Retinal degenerative disorders, such as age-related macular degeneration (AMD), are one of the leading causes of blindness worldwide, however, treatments to completely stop the progression of these debilitating conditions are non-existent. Researchers require sophisticated models that can accurately represent the native structure of human retinal tissue to study these disorders. Current in vitro models used to study the retina are limited in their ability to fully recapitulate the structure and function of the retina, Bruch's membrane and the underlying choroid. Recent developments in the field of induced pluripotent stem cell technology has demonstrated the capability of retinal pigment epithelial cells to recapitulate AMD-like pathology. However, such studies utilise unsophisticated, bio-inert membranes to act as Bruch's membrane and support iPSC-derived retinal cells. This review presents a concise summary of the properties and function of the Bruch's membrane-retinal pigment epithelium complex, the initial pathogenic site of AMD as well as the current status for materials and fabrication approaches used to generate in vitro models of this complex tissue. Finally, this review explores required advances in the field of in vitro retinal modelling. STATEMENT OF SIGNIFICANCE: Retinal degenerative disorders such as age-related macular degeneration are worldwide leading causes of blindness. Previous attempts to model the Bruch's membrane-retinal pigment epithelial complex, the initial pathogenic site of age-related macular degeneration, have lacked the sophistication to elucidate valuable insights into disease mechanisms. Here we provide a detailed account of the morphological, physical and chemical properties of Bruch's membrane which may aid the fabrication of more sophisticated and physiologically accurate in vitro models of the retina, as well as various fabrication techniques to recreate this structure. This review also further highlights some recent advances in some additional challenging aspects of retinal tissue modelling including integrated fluid flow and photoreceptor alignment.
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Biomimética , Lâmina Basilar da Corioide/citologia , Comunicação Celular , Modelos Biológicos , Retina/citologia , Fenômenos Biomecânicos , HumanosRESUMO
The synthesis of a series of tricyclic antagonists for the prostaglandin D(2) receptor DP2 (CRTH2) is disclosed. The activities of the compounds were evaluated in a human DP2 binding assay and a human whole blood eosinophil shape change assay. Potential metabolic liabilities of the compounds were addressed through in vitro CYP studies. The lead compound was demonstrated to have efficacy in a mouse model of allergic rhinitis following oral dosing.
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Antialérgicos/química , Anti-Inflamatórios/química , Compostos Heterocíclicos com 3 Anéis/química , Receptores Imunológicos/antagonistas & inibidores , Receptores de Prostaglandina/antagonistas & inibidores , Rinite Alérgica Perene/tratamento farmacológico , Animais , Antialérgicos/síntese química , Antialérgicos/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Modelos Animais de Doenças , Feminino , Compostos Heterocíclicos com 3 Anéis/síntese química , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Camundongos , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismoRESUMO
OBJECTIVE: To evaluate maternal and neonatal outcomes among scheduled versus unscheduled deliveries in cases of prenatally diagnosed, pathologically proven placenta accreta. STUDY DESIGN: Retrospective cohort of placenta accreta cases delivered in five University of California hospitals. RESULTS: Of 151 cases of histopathologically proven placenta accreta, 82% were prenatally diagnosed. Sixty-seven percent of women underwent scheduled deliveries and 33% were unscheduled. There were no differences in demographics between groups except a higher rate of antepartum bleeding in the unscheduled delivery group (81 versus 53%; p = .003). Scheduled deliveries were associated with a later gestational age at delivery (34.6 versus 32.6 weeks; p = .001), lower blood loss (2.0 versus 2.5 l; p = .04), higher birth weight (2488 versus 2010 g; p < .001), shorter postpartum length of stay (4 versus 5 d; p = .03) and neonatal length of stay (12 versus 20 d; p = .005). CONCLUSION: Despite a prenatal diagnosis of placenta accreta, 1/3 of these cases require unscheduled delivery, portending poorer maternal and neonatal outcomes.
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Cesárea/efeitos adversos , Placenta Acreta/terapia , Resultado da Gravidez/epidemiologia , Adulto , Cesárea/estatística & dados numéricos , Feminino , Idade Gestacional , Humanos , Placenta Acreta/diagnóstico , Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de RiscoRESUMO
The resistance of pathogenic bacteria toward traditional biocidal treatment methods is a growing concern in various settings, including that of water treatment and in the medical industry. As such, advanced antibacterial technologies are needed to prevent infections, against which current antibiotics are failing. This study introduces copper oxide nanoparticles (CuONPs) doped in graphene oxide (GO) as a potential pathogenic bacterial treatment. The aim of the study was to evaluate the antibacterial properties of the GO-CuONP hybridized material against pathogenic Escherichia coli ATCC 8739 (E. coli) and Salmonella typhimurium ATCC 14028 (S. typhimurium). GO was synthesized using a modified Hummer's method and doped with 40% w/w CuONPs using a series of thermal chemical reactions. The resulting hybrids were then characterized using scanning electron microscopic (SEM) and spectroscopic studies. These studies revealed that the hybrid material was considerably altered by the inclusion of CuONPs. The live and dead bacteria attached to the GO-CuONP material were detected using confocal laser scanning microscopy (CLSM). The antibacterial activity assay of the GO-CuONP material was conducted using a standard plate count method. Importantly, the GO-CuONP nanocomposite was determined to be an effective antibacterial nanomaterial, significantly inhibiting the growth of both E. coli and S. typhimurium bacteria compared to that observed on the pristine GO material. This study suggests that GO-CuONP composites are a promising high-efficacy antibacterial nanomaterial.
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Opiate dependence and withdrawal have long been hypothesized to enhance the reinforcing effects of opiates; however, opiate agonist self-administration in these states has yet to be systematically assessed. To address this issue, the reinforcing property of the short-acting mu-opioid agonist, remifentanil, was assessed in morphine-dependent (MD), morphine-dependent and -withdrawn (MW), and nondependent, control (C) rats. Dependence was established by twice daily administration of increasing doses of morphine for 4 days (10, 20, 30, and 40 mg/kg s.c.) and then maintained with a daily injection of the large dose. Morphine deprivation-induced withdrawal (defined by weight loss and hyperalgesia) was apparent 24, but not 12, h after morphine treatment. Remifentanil self-administration (0.4, 0.8, 1.6, 3.2, or 6.4 mug/kg/infusion) was assessed over 20 successive, daily, 1-h sessions, either 12 or 24 h after the maintenance dose of morphine. Compared with the control group, the MD group demonstrated suppressed remifentanil self-administration, whereas the MW group exhibited enhanced responding for every dose of remifentanil. The increased responding observed in the MW group compared with the control and MD groups resulted in an upward shift in the remifentanil dose-response curve, an effect that was expressed only after repeated exposure to the contingency, demonstrating that morphine withdrawal ultimately enhances the reinforcing effects of remifentanil.