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1.
One Health ; 13: 100343, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34805473

RESUMO

Introduction: The negative impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health and physical activity is well reported. While prior studies showed a positive influence of pet ownership on physical activity and mental health, the interactions between the pandemic and pet ownership are not well studied. Objective: To determine the association between pet ownership, physical activity levels and mental health during the COVID-19 pandemic. Materials and methods: A cross-sectional study was conducted from May 19 to July 13, 2020 among Singapore residents aged 21 to 64 years through a previously published questionnaire. Inverse probability treatment weighting was used to develop mixed-effects models for outcome comparisons. We recorded participant data on pet ownership, duration and intensity of physical activity, and RAND 36-item Health Survey mental health domains during the COVID-19 pandemic. Results: The questionnaire was completed by 431 pet owners and 103 non-pet owners. A greater proportion of pet owners were female, non-married, employed and owned pets in the past. Pet owners reported 31.8 (95% CI 13.6 to 50; p = .001) more minutes per week of mild-intensity physical activity compared to non-pet owners. No statistically significant differences were found for moderate- and vigorous-intensity physical activity. Pet owners had better emotional well-being (ꞵ = 9.66, 95% CI 4.97 to 14.4; p < .001), energy (ꞵ = 8.29, 95% CI 3.46 to 13.1; p = .001) and social functioning (ꞵ = 11.2, 95% CI 5.03 to 17.4; p < .001) scores than non-pet owners. However, no statistically significant difference was observed for general health scores. Pet owner physical activity levels, general health, emotional well-being and energy scores correlated positively with pet attachment scores. Conclusion: Pet ownership was associated with greater physical activity levels and better mental health, particularly in main caregivers with higher pet attachment scores. These findings suggest that pet ownership is beneficial to physical and mental well-being during periods of social isolation amidst a global pandemic.

2.
Nat Commun ; 12(1): 4999, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404769

RESUMO

The type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3-/- mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.


Assuntos
Antibacterianos/farmacologia , Listeria/efeitos dos fármacos , Listeriose/imunologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Fagócitos/imunologia , Fagócitos/microbiologia , Animais , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno , Interferon Tipo I/metabolismo , Listeria monocytogenes/imunologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fagossomos/imunologia , Células RAW 264.7 , Transcriptoma , Fatores de Virulência , Internalização do Vírus/efeitos dos fármacos
3.
J Orthop Trauma ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34282094

RESUMO

OBJECTIVES: The review aims to pool together the different surgical managements and outcomes of missed paediatric Monteggia fractures. DATA SOURCES: A systematic review was conducted using PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and The Cochrane Library from inception through 02 March 2020. The keywords were "Monteggia fracture", "missed Monteggia", "neglected Monteggia", "chronic Monteggia" and "chronic radial head dislocation". STUDY SELECTION: All original human studies on missed paediatric Monteggia fractures were included. Congenital Monteggia fractures and isolated radial head dislocations were excluded. DATA EXTRACTION: The revised Methodological Index for Non-Randomised Studies tool was used to assess the quality of studies. DATA SYNTHESIS: Each patient's data was retrieved individually. Chi-square test and Fisher's exact test were used to analyse the difference in outcomes for different surgical managements. Multivariate analysis was performed for variables that were significant on univariate analysis. CONCLUSIONS: 30 studies with 600 patients were included. Proximal ulnar osteotomies (p = 0.016) and the absence of transcapitellar pinning (p = 0.001) were the most significant predictors for eventual reduction of radial head. Other surgical management variables were not significant predictors. These include open or closed reduction, approach of radial head reduction, presence or absence of ulnar osteotomy, presence or absence of lengthening, angular correction, overcorrection or bone grafting of ulnar osteotomy, type of fixation for ulnar osteotomy, presence or absence of radial osteotomy, presence or absence of annular ligament repair or reconstruction and repair or reconstruction of annular ligament. LEVEL OF EVIDENCE: Level IV. See Instructions for Authors for a complete description of levels of evidence.

5.
Ann Surg Oncol ; 28(5): 2474-2482, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33393052

RESUMO

BACKGROUND: Outcomes commonly used to ascertain success of metastatic spine tumour surgery (MSTS) are 30-day complications/mortality and overall/disease-free survival. We believe a new, effective outcome indicator after MSTS would be the absence of unplanned hospital readmission (UHR) after index discharge. We introduce the concept of readmission-free survival (ReAFS), defined as 'the time duration between hospital discharge after index operation and first UHR or death'. The aim of this study is to identify factors influencing ReAFS in MSTS patients. PATIENTS AND METHODS: We retrospectively analysed 266 consecutive patients who underwent MSTS between 2005 and 2016. Demographics, oncological characteristics, procedural, preoperative and postoperative details were collected. ReAFS of patients within 2 years or until death was reviewed. Perioperative factors predictive of reduced ReAFS were evaluated using multivariate regression analysis. RESULTS: Of 266 patients, 230 met criteria for analysis. A total of 201 had UHR, whilst 1 in 8 (29/230) had no UHR. Multivariate analysis revealed that haemoglobin ≥ 12 g/dL, ECOG score of ≤ 2, primary prostate, breast and haematological cancers, comorbidities ≤ 3, absence of preoperative radiotherapy and shorter postoperative length of stay significantly prolonged the time to first UHR. CONCLUSIONS: Readmission-free survival is a novel concept in MSTS, which relies on patients' general condition, appropriateness of interventional procedures and underlying disease burden. Additionally, it may indicate the successful combination of a multi-disciplinary treatment approach. This information will allow oncologists and surgeons to identify patients who may benefit from increased surveillance following discharge to increase ReAFS. We envisage that ReAFS is a concept that can be extended to other surgical oncological fields.


Assuntos
Neoplasias , Complicações Pós-Operatórias , Humanos , Tempo de Internação , Masculino , Readmissão do Paciente , Estudos Retrospectivos , Fatores de Risco , Coluna Vertebral , Análise de Sobrevida
6.
Eur Spine J ; 30(10): 2887-2895, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33459874

RESUMO

PURPOSE: The aim of this study was to investigate rates, causes, and risk factors of unplanned hospital readmissions (UHR) within 30 days, 90 days, 1 year and 2 years after metastatic spine tumour surgery (MSTS) to augment multi-disciplinary treatment planning and improve patient education. METHODS: We retrospectively reviewed 272-patients who underwent MSTS between 2005 and 2016. Hospital records were utilised to obtain demographics, oncological, procedural details, and postoperative outcomes. All UHR within 2 years were reviewed. Primary outcomes were rates, causes, and risk factors of UHR. Risk factors for UHR were evaluated utilising multivariate logistic regression analysis. RESULTS: Thirty-day, 90 day, 1 year, and 2 year UHR-rates after MSTS were 17.2%, 31.1%, 46.2%, and 52.7%, respectively. Lung cancer primaries had the highest UHR-events (24.7%) whilst renal/thyroid displayed the least (6.6%). Disease-related causes (16.2%) were the most common reason for readmissions across all timeframes, followed by respiratory (13.7%) and progression of metastatic spine disease (12.7%). Urological conditions accounted for majority of readmissions within 30-days; disease-related causes, symptomatic spinal metastases, and respiratory conditions represented the most common causes at 30-90 days, 90 days-1 year, and 1-2 years, respectively. An ECOG >1 (p = 0.057), CCI >7 (p = 0.01), and primary lung tumour (p = 0.02) significantly increased UHR-risk on multivariate analysis. CONCLUSION: Seventy-four percent of patients had at least one UHR within 2 years of MSTS and majority were secondary to disease-related causes. Majority of first UHR occurred between 30 and 90 days post-surgery. Local disease progression and overall disease progression account for the highest UHR-events at 90 days-1 year and 1-2 year timeframes, respectively. We define UHR in specific timeframes, thus enabling better surveillance and reducing unnecessary morbidity.


Assuntos
Neoplasias , Readmissão do Paciente , Humanos , Estudos Retrospectivos , Coluna Vertebral , Fatores de Tempo
7.
Asian J Surg ; 44(1): 307-312, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32863145

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) is a structured programme using a multimodal, evidence-based approach to improve post-operative outcomes. Successful implementation of ERAS can be challenging. We aimed to evaluate our initial experience with colorectal ERAS and explore the perspectives of specialist doctors and nurses. METHODS: From 1 June 2017 to 31 December 2017, all patients who underwent elective colorectal resection and met the ERAS inclusion criteria at the Department of Colorectal Surgery, Singapore General Hospital, were included in the study. Short-term outcomes were compared between patients with >70% compliance to key ERAS components versus those with ≤70% compliance. Department staff were surveyed via questionnaire in July 2019. RESULTS: Three hundred and fifteen patients were included in study. >70% ERAS compliance rate was achieved in 84 patients (26.7%). A higher compliance rate resulted in a significantly shorter length of stay of 6 (IQR 5-8) days vs. 7 (IQR 6-9.5) days (p = 0.025) and lower readmission rate of 3.6% (n = 3) vs. 4.8% (n = 11) (p = 0.042), as well as a trend towards reduced complication rate of 15.4% (n = 13) vs. 22.0% (n = 51) and earlier return to gastrointestinal function. There was a 100% questionnaire response amongst all 12 colorectal surgeons and 5 colorectal resident nurse practitioners. CONCLUSION: Increased adherence to the components of ERAS results in better early outcomes and may have long-term benefits on survival. Effective communication and professional support for the ERAS multi-disciplinary team, as well as understanding healthcare workers' concerns and addressing long-standing practices, is essential for successful implementation of the programme.


Assuntos
Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Eletivos , Recuperação Pós-Cirúrgica Melhorada , Enfermeiras e Enfermeiros , Cirurgiões , Idoso , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Singapura , Inquéritos e Questionários , Resultado do Tratamento
8.
J Orthop Trauma ; 35(7): e234-e240, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33252447

RESUMO

OBJECTIVES: We hypothesize that in adequately resuscitated borderline polytrauma patients with long bone fractures (femur and tibia) or pelvic fractures, early (within 4 days) definitive stabilization (EDS) can be performed without an increase in postoperative ventilation and postoperative complications. DESIGN: Retrospective cohort study. SETTING: Level 1 trauma center. PATIENTS: In total, 103 patients were included in this study; of whom, 18 (17.5%) were female and 85 (82.5%) were male. These patients were borderline trauma patients who had the following parameters before definitive surgery, normal coagulation profile, lactate of <2.5 mmol/L, pH of ≥7.25, and base excess of ≥5.5. INTERVENTION: These patients were treated according to Early Total Care, definitive surgery on day of admission, or Damage Control Orthopaedics principles, temporizing external fixation followed by definitive surgery at a later date. Timing of definitive surgical fixation was recorded as EDS or late definitive surgical fixation (>4 days). MAIN OUTCOME MEASURES: Primary outcome measured was the duration of ventilation more than 3 days post definitive surgery and presence of postoperative complications. RESULTS: Thirty-five patients (34.0%) received Early Total Care, whereas 68 (66.0%) patients were treated with Damage Control Orthopaedics. In total, 51 (49.5%) of all patients had late definitive surgery, whereas 52 patients (50.5%) had EDS. On logistic regression, the following factors were found to be predictive of higher rates of postoperative ventilation ≥ 3 days, units of blood transfused, and time to definitive surgery > 4 days. Increased age, head abbreviated injury score of 3 or more and time to definitive surgery were found to be associated with an increased risk of postoperative complications. CONCLUSIONS: Borderline polytrauma patients with no severe soft tissue injuries, such as chest or head injuries, may be treated with EDS if adequately resuscitated with no increase in need for postoperative ventilation and complications. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Fraturas Ósseas , Traumatismo Múltiplo , Feminino , Fixação de Fratura , Fraturas Ósseas/cirurgia , Humanos , Masculino , Traumatismo Múltiplo/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
9.
J Immunol ; 206(2): 323-328, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33288542

RESUMO

The NOX2 NADPH oxidase (NOX2) produces reactive oxygen species to kill phagosome-confined bacteria. However, we previously showed that Listeria monocytogenes is able to avoid the NOX2 activity in phagosomes and escape to the cytosol. Thus, despite the established role of NOX2 limiting L. monocytogenes infection in mice, the underlying mechanisms of this antibacterial activity remain unclear. In this article, we report that NOX2 controls systemic L. monocytogenes spread through modulation of the type I IFN response, which is known to be exploited by L. monocytogenes during infection. NOX2 deficiency results in increased expression of IFN-stimulated genes in response to type I IFN and leads to 1) promotion of cell-to-cell spread by L. monocytogenes, 2) defective leukocyte recruitment to infection foci, and 3) production of anti-inflammatory effectors IL-10 and thioredoxin 1. Our findings report a novel antimicrobial role for NOX2 through modulation of type I IFN responses to control bacterial dissemination.


Assuntos
Inflamação/imunologia , Interferon Tipo I/metabolismo , Leucócitos/imunologia , Listeria monocytogenes/fisiologia , Listeriose/imunologia , Macrófagos/metabolismo , NADPH Oxidase 2/metabolismo , Animais , Movimento Celular , Células Cultivadas , Interleucina-10/metabolismo , Listeriose/transmissão , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 2/genética , Tiorredoxinas
10.
Sci Rep ; 10(1): 19898, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199739

RESUMO

Although existing literature increasingly suggests a positive influence of pet ownership on human physical activity levels, results from many European, American, and Japanese studies have been inconsistent. How pet ownership impacts mental health and atopy is likewise controversial and whether distinct demographic subgroups experience differential effects is unclear. This cross-sectional study surveyed participants (n = 823) via a self-administered online questionnaire. Comparisons of outcomes between pet owners and non-pet owners with subgroup analyses were performed within a propensity score-matched subset (n = 566) of respondents. There were no differences in physical activity levels or mental health scores between pet owners and non-pet owners. In subgroup analyses, compared to non-pet owners, main pet caregivers reported 14.1 (95% CI 2.79-25.3) and 19.0 (95% CI 4.70-33.3) more minutes per week of moderate- and vigorous-intensity physical activity respectively and higher SF-36 emotional well-being (ß = 2.7, 95% CI 0.100-5.32) and energy scores (ß = 3.8, 95% CI 0.410-7.27). Age was a significant effect modifier of the association between pet ownership and emotional well-being, energy and social functioning scores, with greater scores above the ages of 39, 35 and 39 years old respectively (interaction p = 0.043, 0.044, 0.042). Finally, pet acquisition was associated with worsening of allergic rhinitis, while pet ownership cessation was associated with improvement of allergic rhinitis and eczema symptoms. To our knowledge, this is the first study addressing the public health impact of pet ownership in Southeast Asia and its findings add contextual nuance to suggest potential benefits derived from pet ownership.


Assuntos
Eczema/prevenção & controle , Exercício Físico , Comportamentos Relacionados com a Saúde , Vínculo Humano-Animal , Saúde Mental , Propriedade , Rinite Alérgica/prevenção & controle , Adulto , Animais , Estudos Transversais , Eczema/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Animais de Estimação , Rinite Alérgica/epidemiologia , Singapura/epidemiologia , Adulto Jovem
11.
Front Immunol ; 11: 580968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013934

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has been on a global rise. While animal models have rendered valuable insights to the pathogenesis of NAFLD, discrepancy with patient data still exists. Since non-alcoholic steatohepatitis (NASH) involves chronic inflammation, and CD4+ T cell infiltration of the liver is characteristic of NASH patients, we established and characterized a humanized mouse model to identify human-specific immune response(s) associated with NAFLD progression. Immunodeficient mice engrafted with human immune cells (HIL mice) were fed with high fat and high calorie (HFHC) or chow diet for 20 weeks. Liver histology and immune profile of HIL mice were analyzed and compared with patient data. HIL mice on HFHC diet developed steatosis, inflammation and fibrosis of the liver. Human CD4+ central and effector memory T cells increased within the liver and in the peripheral blood of our HIL mice, accompanied by marked up-regulation of pro-inflammatory cytokines (IL-17A and IFNγ). In vivo depletion of human CD4+ T cells in HIL mice reduced liver inflammation and fibrosis, but not steatosis. Our results highlight CD4+ memory T cell subsets as important drivers of NAFLD progression from steatosis to fibrosis and provides a humanized mouse model for pre-clinical evaluation of potential therapeutics.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Cirrose Hepática Experimental/etiologia , Cirrose Hepática Experimental/imunologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Animais , Linfócitos T CD4-Positivos/patologia , Citocinas/sangue , Dieta Hiperlipídica/efeitos adversos , Feminino , Células-Tronco Fetais/transplante , Hepatócitos/transplante , Xenoenxertos , Humanos , Subunidade gama Comum de Receptores de Interleucina/deficiência , Subunidade gama Comum de Receptores de Interleucina/genética , Cirrose Hepática Experimental/patologia , Depleção Linfocítica , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Hepatopatia Gordurosa não Alcoólica/patologia
12.
Biomed Opt Express ; 11(7): 3507-3522, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33014547

RESUMO

The accumulation of potassium (K+) in the tumor microenvironment (TME) has been recently shown to inhibit immune cell efficacy, and thus immunotherapy. Despite the abundance of K+ in the body, few ways exist to measure it in vivo. To address this technology gap, we combine an optical K+ nanosensor with photoacoustic (PA) imaging. Using multi-wavelength deconvolution, we are able to quantitatively evaluate the TME K+ concentration in vivo, and its distribution. Significantly elevated K+ levels were found in the TME, with an average concentration of approximately 29 mM, compared to 19 mM found in muscle. These PA measurements were confirmed by extraction of the tumor interstitial fluid and subsequent measurement via inductively coupled plasma mass spectrometry.

13.
Rheumatol Int ; 40(11): 1825-1834, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32776160

RESUMO

OBJECTIVE: To describe the prevalence of and evaluate the factors associated with fatigue patients with psoriatic arthritis (PsA) in an Asian population. METHODS: We used baseline data from a registry of patients with PsA attending an outpatient clinic of a tertiary hospital in Singapore. Demographic data and disease characteristics were evaluated. Fatigue was assessed by question one of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI-F) and the vitality domain of the Medical Outcome Survey, Short-Form 36 (SF-36 VT). We evaluated clusters of variables, and individual variables in association with fatigue. RESULTS: We included 131 patients (50.4% men, 63.4% Chinese, median PsA duration 21.0 months) with completed data for fatigue. Forty-five patients (34%) experienced severe fatigue (defined by BASDAI-F > 5/10). We used principal component analysis and identified five clusters of variables that explained 62.9% of the variance of all factors. Of these, disease activity and impact, and disease chronicity were significantly associated with BASDAI-F and SF-36 VT. In multivariable analyses, back pain, peripheral joint pain and patient global assessment were associated with BASDAI-F, whereas peripheral joint pain and mental health were associated with SF-36 VT. CONCLUSION: PsA-associated fatigue is prevalent in this Asian PsA cohort and is associated with disease activity, impact and chronicity.


Assuntos
Artrite Psoriásica/fisiopatologia , Fadiga/epidemiologia , Fadiga/fisiopatologia , Adulto , Fatores Etários , Dor nas Costas/epidemiologia , Índice de Massa Corporal , Estudos Transversais , Grupos Étnicos , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Análise Multivariada , Medidas de Resultados Relatados pelo Paciente , Prevalência , Análise de Componente Principal , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Singapura/epidemiologia , Fatores de Tempo
14.
Stem Cell Reports ; 14(5): 818-827, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32302554

RESUMO

Spermatogenesis relies on exquisite stem cell homeostasis, the carefully balanced self-renewal and differentiation of spermatogonial stem cells (SSCs). Disturbing this equilibrium will likely manifest through sub- or infertility, a global health issue with often idiopathic presentation. In this respect, disease phenotypes caused by haploinsufficiency of otherwise vital developmental genes are of particular interest. Here, we show that mice heterozygous for Trim28, an essential epigenetic regulator, suffer gradual testicular degeneration. Contrary to previous reports we detect Trim28 expression in spermatogonia, albeit at low levels. Further reduction through Trim28 heterozygosity increases the propensity of SSCs to differentiate at the cost of self-renewal.


Assuntos
Infertilidade Masculina/genética , Espermatogônias/metabolismo , Proteína 28 com Motivo Tripartido/genética , Animais , Haploinsuficiência , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espermatogênese , Espermatogônias/citologia
15.
Small ; 16(4): e1905519, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31885136

RESUMO

Materials made by directed self-assembly of colloids can exhibit a rich spectrum of optical phenomena, including photonic bandgaps, coherent scattering, collective plasmonic resonance, and wave guiding. The assembly of colloidal particles with spatial selectivity is critical for studying these phenomena and for practical device fabrication. While there are well-established techniques for patterning colloidal crystals, these often require multiple steps including the fabrication of a physical template for masking, etching, stamping, or directing dewetting. Here, the direct-writing of colloidal suspensions is presented as a technique for fabrication of iridescent colloidal crystals in arbitrary 2D patterns. Leveraging the principles of convective assembly, the process can be optimized for high writing speeds (≈600 µm s-1 ) at mild process temperature (30 °C) while maintaining long-range (cm-scale) order in the colloidal crystals. The crystals exhibit structural color by grating diffraction, and analysis of diffraction allows particle size, relative grain size, and grain orientation to be deduced. The effect of write trajectory on particle ordering is discussed and insights for developing 3D printing techniques for colloidal crystals via layer-wise printing and sintering are provided.

16.
ACS Nano ; 13(12): 14024-14032, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31820930

RESUMO

Lifetime imaging methods using phosphorescence quenching by oxygen for molecular oxygen concentration measurement have been developed and used for noninvasive oxygen monitoring. This study reports photoacoustic (PA) oxygen imaging powered by polyacrylamide (PAAm) hydrogel nanoparticles (NP) which offer advantages including improved biocompatibility, reduced toxicity, and active tumor targeting. A known oxygen indicator, oxyphor G2, was conjugated with the matrix of the NPs, giving G2-PAA NPs, followed by PEGylation for biocompatibility and F3 surface modification for tumor targeting. Using two lasers providing pump and probe pulses, respectively, PA imaging was performed so as to quantitatively map the oxygen concentration in biological tissues in vivo, including cancer tumors and normal thigh muscles. Furthermore, via the imaging at the pump wavelength and two additional wavelengths, the accumulation of the G2-PAA NPs in the tumors were also determined. The successful imaging experiment accomplished on animal models renders a method for in vivo noninvasive imaging and assessment of hypoxic tumor microenvironments, which is critical for assessing cancer progression, metastasis, and treatment.


Assuntos
Resinas Acrílicas/química , Metaloporfirinas/química , Nanosferas/química , Neoplasias/diagnóstico por imagem , Oxigênio/análise , Técnicas Fotoacústicas , Animais , Calibragem , Feminino , Imageamento Tridimensional , Metaloporfirinas/síntese química , Camundongos Nus , Neoplasias/patologia
17.
J Biol Chem ; 294(44): 16172-16185, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31515271

RESUMO

Connections between deficient autophagy and insulin resistance have emerged, however, the mechanism through which reduced autophagy impairs insulin-signaling remains unknown. We examined mouse embryonic fibroblasts lacking Atg16l1 (ATG16L1 KO mouse embryonic fibroblasts (MEFs)), an essential autophagy gene, and observed deficient insulin and insulin-like growth factor-1 signaling. ATG16L1 KO MEFs displayed reduced protein content of insulin receptor substrate-1 (IRS1), pivotal to insulin signaling, whereas IRS1myc overexpression recovered downstream insulin signaling. Endogenous IRS1 protein content and insulin signaling were restored in ATG16L1 KO mouse embryonic fibroblasts (MEF) upon proteasome inhibition. Through proximity-dependent biotin identification (BioID) and co-immunoprecipitation, we found that Kelch-like proteins KLHL9 and KLHL13, which together form an E3 ubiquitin (Ub) ligase complex with cullin 3 (CUL3), are novel IRS1 interactors. Expression of Klhl9 and Klhl13 was elevated in ATG16L1 KO MEFs and siRNA-mediated knockdown of Klhl9, Klhl13, or Cul3 recovered IRS1 expression. Moreover, Klhl13 and Cul3 knockdown increased insulin signaling. Notably, adipose tissue of high-fat fed mice displayed lower Atg16l1 mRNA expression and IRS1 protein content, and adipose tissue KLHL13 and CUL3 expression positively correlated to body mass index in humans. We propose that ATG16L1 deficiency evokes insulin resistance through induction of Klhl9 and Klhl13, which, in complex with Cul3, promote proteasomal IRS1 degradation.


Assuntos
Proteínas Relacionadas à Autofagia/deficiência , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Animais , Autofagia/fisiologia , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Culina/metabolismo , Fibroblastos/metabolismo , Genes Reguladores , Células HEK293 , Humanos , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas/metabolismo , Transdução de Sinais , Complexos Ubiquitina-Proteína Ligase/metabolismo
18.
Proc Math Phys Eng Sci ; 475(2227): 20190207, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31423101

RESUMO

Fluid-filled shells are near-ubiquitous in natural and engineered structures-a familiar example is that of glass harps comprising partially filled wineglasses or glass bowls, whose acoustic properties are readily noticeable. Existing theories modelling the mechanical properties of such systems under vibrational load either vastly simplify shell geometry and oscillatory modal shapes to admit analytical solutions or rely on finite-element black-box computations for general cases, the former yielding poor accuracy and the latter offering limited tractability and physical insight. In the present study, we derive a theoretical framework encompassing elastic shell deformation with structural and viscous dissipation, accommodating arbitrary axisymmetric shell geometries and fluid levels; reductions to closed-form solutions under specific assumptions are shown to be possible. The theory is extensively verified against a range of geometries, fluid levels and fluid viscosities in experiments; an extension of the model encompassing additional solid objects within the fluid-filled shell is also considered and verified. The presented theoretical advance in describing vibrational response is relevant in performance evaluation for engineered structures and quality validation in manufacturing.

19.
PLoS One ; 14(7): e0219655, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31306463

RESUMO

Prostate cancer was the most common form and had the second highest death rate of male cancer in the United States in 2015. Current diagnosis techniques, such as prostate-specific antigen tests, transrectal ultrasound scans, and biopsies, are often inconclusive, and in the latter case, invasive. Here, we explore the use of clofazimine hydrochloride nanoparticles (CFZ-HCl NPs), a repurposed formulation from an FDA-approved antimycobacterial agent, as a photoacoustic contrast agent for the evaluation of prostate cancer due to its macrophage-targeting capabilities and high optical absorbance at 495 nm. Using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, our results indicate a preferential accumulation of intravenously injected CFZ-HCl NPs in cancerous prostates over normal prostates. Differences in accumulation of CFZ-HCl NPs between cancerous and normal prostates were determined using a two-wavelength unmixing technique via ex vivo photoacoustic imaging. Thus, intravenous injection of CFZ-HCl NPs leads to differences in the interactions of the particles with cancerous vs normal prostates, while allowing for photoacoustic detection and analysis of prostate cancer. These findings could lead to the development of a new noninvasive technique for the detection and monitoring of prostate cancer progression in an animal model that can potentially be translated to human patients.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Cloretos/farmacocinética , Clofazimina/farmacocinética , Nanopartículas/química , Próstata/efeitos dos fármacos , Neoplasias da Próstata/diagnóstico por imagem , Animais , Meios de Contraste/farmacocinética , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência , Nanomedicina/métodos , Técnicas Fotoacústicas , Sensibilidade e Especificidade
20.
J Cell Biol ; 218(9): 2896-2918, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31350280

RESUMO

Meiosis generates four genetically distinct haploid gametes over the course of two reductional cell divisions. Meiotic divisions are characterized by the coordinated deposition and removal of various epigenetic marks. Here we propose that nuclear respiratory factor 1 (NRF1) regulates transcription of euchromatic histone methyltransferase 1 (EHMT1) to ensure normal patterns of H3K9 methylation during meiotic prophase I. We demonstrate that cyclin-dependent kinase (CDK2) can bind to the promoters of a number of genes in male germ cells including that of Ehmt1 through interaction with the NRF1 transcription factor. Our data indicate that CDK2-mediated phosphorylation of NRF1 can occur at two distinct serine residues and negatively regulates NRF1 DNA binding activity in vitro. Furthermore, induced deletion of Cdk2 in spermatocytes results in increased expression of many NRF1 target genes including Ehmt1 We hypothesize that the regulation of NRF1 transcriptional activity by CDK2 may allow the modulation of Ehmt1 expression, therefore controlling the dynamic methylation of H3K9 during meiotic prophase.


Assuntos
Quinase 2 Dependente de Ciclina/metabolismo , Regulação Enzimológica da Expressão Gênica , Histona-Lisina N-Metiltransferase/biossíntese , Prófase Meiótica I/fisiologia , Fator 1 Nuclear Respiratório/metabolismo , Espermatócitos/metabolismo , Animais , Quinase 2 Dependente de Ciclina/genética , Deleção de Genes , Histona-Lisina N-Metiltransferase/genética , Masculino , Camundongos , Camundongos Knockout , Fator 1 Nuclear Respiratório/genética , Espermatócitos/citologia
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