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1.
Mol Cell ; 82(1): 123-139.e7, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34910943

RESUMO

Mediator kinases (CDK8/19) are transcriptional regulators broadly implicated in cancer. Despite their central role in fine-tuning gene-expression programs, we find complete loss of CDK8/19 is tolerated in colorectal cancer (CRC) cells. Using orthogonal functional genomic and pharmacological screens, we identify BET protein inhibition as a distinct vulnerability in CDK8/19-depleted cells. Combined CDK8/19 and BET inhibition led to synergistic growth retardation in human and mouse models of CRC. Strikingly, depletion of CDK8/19 in these cells led to global repression of RNA polymerase II (Pol II) promoter occupancy and transcription. Concurrently, loss of Mediator kinase led to a profound increase in MED12 and BRD4 co-occupancy at enhancer elements and increased dependence on BET proteins for the transcriptional output of cell-essential genes. In total, this work demonstrates a synthetic lethal interaction between Mediator kinase and BET proteins and exposes a therapeutic vulnerability that can be targeted using combination therapies.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Neoplasias Colorretais/enzimologia , Quinase 8 Dependente de Ciclina/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Complexo Mediador/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sítios de Ligação , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Quinase 8 Dependente de Ciclina/genética , Quinases Ciclina-Dependentes/genética , Elementos Facilitadores Genéticos , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Masculino , Complexo Mediador/antagonistas & inibidores , Complexo Mediador/genética , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Nus , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Inibidores de Proteínas Quinases/farmacologia , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Transdução de Sinais , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Transcrição Gênica , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
2.
J Card Surg ; 37(4): 725-731, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35060186

RESUMO

BACKGROUND: This study was conducted to evaluate the surgical results of the arterial switch operation for Taussig-Bing variants, at a single institution in a lower-middle income country. METHODS: Between June 2010 and December 2018, all consecutive patients diagnosed with Taussig-Bing variants who underwent the arterial switch operation and ventricular septal defect closure were included in the study. RESULTS: A total of 72 patients of Taussig-Bing variants underwent arterial switch operation and ventricular septal defect closure. There were 10 early deaths (13.9%) and 2 late deaths (2.8%). Intraoperative ventricular septal defect enlargement (hazard ratio [HR] 7.23, 95% confidence interval [CI] 3.1294-16.7167; p < .001), secondary aortic cross-clamping (HR 28.38, 95% CI 4.8427-166.3484; p < .001), postoperative pneumonia (HR 5.64, 95% CI 1.2724-24.9917; p = .023), and postoperative sepsis (HR 5.28, 95% CI 1.3512-20.6553; p = .017) were risk factors for overall mortality by competing risk analysis. Sixty patients (83.3%) required septoparietal trabeculation division/resection during the arterial switch operation in an attempt to avoid right ventricular outflow tract obstruction. The reoperation rate for right ventricular outflow tract obstruction at last follow up was 6% (three patients). The estimated freedom from reoperation for right ventricular outflow tract obstruction at 1, 5, and 9 years was 98.3%, 91.9%, and 91.9%, respectively. CONCLUSIONS: The results of arterial switch operation for Taussig-Bing variants were satisfactory in the operative setting of a lower-middle income country, and performing extensive septoparietal trabeculation division might reduce the reintervention rate for right ventricular outflow tract obstruction in these patients.


Assuntos
Transposição das Grandes Artérias , Dupla Via de Saída do Ventrículo Direito , Transposição dos Grandes Vasos , Transposição das Grandes Artérias/efeitos adversos , Dupla Via de Saída do Ventrículo Direito/cirurgia , Seguimentos , Humanos , Lactente , Reoperação , Estudos Retrospectivos , Transposição dos Grandes Vasos/complicações , Resultado do Tratamento
3.
Sex Health ; 18(1): 104-115, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33653505

RESUMO

Background HIV prevalence among men who have sex with men (MSM) and transgender women (TGW) in Vietnam is high, whereas coverage of effective HIV prevention services has been inadequate. Studies have measured MSM and TGW demand for pre-exposure prophylaxis (PrEP) services, which led to the design of the first ever PrEP program in Vietnam, Prepped for PrEP (P4P). METHODS: In March 2017, PrEP services were offered in Ho Chi Minh City as part of the P4P demonstration project, enabling same-day enrolment in three key population (KP)-led clinics and four public clinics. P4P aimed to assess acceptability and feasibility of PrEP services through calculating the rate of PrEP enrolment over time, and quarterly measures of continuation and adherence over an 18-month period. RESULTS: A total of 1069 MSM and 62 TGW were enrolled in P4P. Average monthly PrEP enrolment among MSM increased five-fold from the first 3 months (March-June 2017) to the last 3 months of active enrolment (March-June 2018), whereas for TGW, no increased trend in PrEP enrolment per quarter was seen. Self-reported PrEP adherence was >90% at all time points among MSM, but varied from 11.1% to 88.9% among TGW. PrEP continuation was calculated at months 3, 6, 9, 12, 15 and 18. For MSM, it was 88.7% at month 3, 68.8% at month 12 and 46.6% at month 18, whereas for TGW, it was 87.1%, 54.8% and 52.8%, respectively. Multivariable regression identified that MSM with lower-than-average income (adjusted odds ratio (aOR) 2.38 (95% confidence interval (CI): 1.59-3.54), P = 0.000), aged >30 years (aOR 2.03 (95% CI: 1.30-3.40), P = 0.007) and with an increasing number of sex partners (aOR: 1.06 (1.01-1.11), P = 0.011) had greater odds of remaining on PrEP. For TGW, being aged >30 years was associated with continuing on PrEP (aOR 5.62 (95% CI: 1.05-29.9), P = 0.043). CONCLUSIONS: We found PrEP to be highly acceptable among MSM and moderately acceptable among TGW. Continuation rates were relatively high for the first roll-out of PrEP; however, those aged ≤30 years were much more likely to discontinue services. Scaling-up PrEP through differentiated and community-led and engaged PrEP service delivery will be key to effectively increase access and uptake over the next 5 years.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Pessoas Transgênero , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Vietnã
4.
Opt Express ; 27(12): A725-A737, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31252849

RESUMO

Ultra-narrowband perfect absorbers and emitters are proposed and realized by engineering multiple-beam interference in Gires-Tournois etalon with the presence of low metallic loss. The absorption mechanism and spectral characteristics of the Gires-Tournois resonators are numerically and experimentally investigated for three configurations: dielectric cavity on metal, metal-dielectric-metal resonator, and distributed Bragg reflector (DBR)-dielectric-metal resonator. Narrowband thermal emitters based on the metal-dielectric-metal cavity and (DBR)-dielectric-metal cavity are experimentally demonstrated with an emissivity of 0.8 and 0.82, and a quality factor of 21 and 85, respectively. A DBR-dielectric-metal resonator-based absorber is directly loaded onto a LiTaO 3 film for the first time to constitute an on-chip ultra-narrowband pyroelectric detector with an excellent quality factor of 151 at the absorption band of methane.

5.
New Phytol ; 217(1): 245-260, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29105089

RESUMO

Photosynthetic organisms such as plants, algae and some cyanobacteria synthesize tocochromanols, a group of compounds that encompasses tocopherols and tocotrienols and that exhibits vitamin E activity in animals. While most vitamin E biosynthetic genes have been identified in plant genomes, regulatory genes controlling tocopherol accumulation are currently unknown. We isolated by forward genetics Arabidopsis enhanced vitamin E (eve) mutants that overaccumulate the classic tocopherols and plastochromanol-8, and a tocochromanol unknown in this species. We mapped eve1 and eve4, and identified the unknown Arabidopsis tocochromanol by using a combination of analytical tools. In addition, we determined its biosynthetic pathway with a series of tocochromanol biosynthetic mutants and transgenic lines. eve1 and eve4 are two seed lipid mutants affecting the WRINKLED1 (WRI1) and ACYL-COA:DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1) genes, respectively. The unknown tocochromanol is 11'-12' γ-tocomonoenol, whose biosynthesis is VITAMIN E 1 (VTE1) - and VTE2-dependent and is initiated by the condensation of homogentisate (HGA) and tetrahydrogeranylgeranyl pyrophosphate. This study identifies the first two regulatory genes, WRI1 and DGAT1, that control the synthesis of all tocochromanol forms in seeds, and shows the existence of a metabolic trade-off between lipid and tocochromanol metabolisms. Moreover, it shows that Arabidopsis possesses a tocomonoenol biosynthetic pathway that competes with tocopherol synthesis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Diacilglicerol O-Aciltransferase/metabolismo , Diglicerídeos/metabolismo , Fatores de Transcrição/metabolismo , Vitamina E/metabolismo , Acil Coenzima A/metabolismo , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Vias Biossintéticas , Cromanos/metabolismo , Diacilglicerol O-Aciltransferase/genética , Transferases Intramoleculares/genética , Transferases Intramoleculares/metabolismo , Metabolismo dos Lipídeos , Sementes/enzimologia , Sementes/genética , Tocoferóis/metabolismo , Tocotrienóis/metabolismo , Fatores de Transcrição/genética , Vitamina E/análogos & derivados
6.
AIDS Behav ; 20(Suppl 3): 379-385, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27435074

RESUMO

Globally, transgender women have higher risk for HIV than the general population and men who have sex with men, but there is little data on this population in Vietnam. In 2015 we conducted a biological and behavioral survey of 205 transgender women in Ho Chi Minh City, Vietnam. Factors associated with HIV and syphilis infection were assessed through multivariable logistic regression models. Median age was 25 years (range 18-64). Overall prevalence was 18.0 % for HIV and 17.6 % for syphilis. Factors independently associated with HIV infection included risky alcohol use [adjusted Odds Ratio (aOR) 3.55, 95 % confidence interval (CI) 1.53-8.21], amphetamine stimulant use (aOR 2.90, 95 % CI 1.27-6.61), sex with male sex workers (aOR 4.73, 95 % CI 1.72-13.0), and history of sex with an adult before the age of 18 years (aOR 2.97, 95 % CI 1.06-8.34). Two factors associated with syphilis infection were HIV infection (aOR 2.37, 95 % CI 1.03-5.45) and condomless anal sex with casual partners (aOR 2.27, 95 % CI 1.03-5.00). In order to address the HIV and syphilis epidemics in Vietnamese transgender women, interventions are needed to make HIV and sexually transmitted infection screening and treatment more accessible.


Assuntos
Infecções por HIV/epidemiologia , Comportamento Sexual/estatística & dados numéricos , Sífilis/epidemiologia , Pessoas Transgênero/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Profissionais do Sexo , Parceiros Sexuais , Sexo sem Proteção/estatística & dados numéricos , Vietnã/epidemiologia , Adulto Jovem
7.
P T ; 39(10): 695-715, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25336865

RESUMO

Elevated uric acid levels can cause crystal deposition and may lead to gout, urolithiasis, and urate nephropathy. The authors report on the case of a 34-year-old male whose hyperuricemia was associated with the antituberculous drug pyrazinamide.

8.
Transcult Psychiatry ; : 13634615241228071, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38529626

RESUMO

Acceptance and Commitment Therapy (ACT) is an empirically supported psychotherapy that offers promise for the mental health of minoritised ethnic populations. Given the diversity of those presenting to inner-city services and barriers to accessing appropriate mental healthcare, we sought to develop a culturally syntonic ACT intervention for UK Vietnamese refugee communities in a practice-based partnership project between a National Health Service and local third-sector service in East London. The aim was to explore the feasibility, acceptability and impact of the adapted intervention to inform culturally inclusive clinical practice and future research. We outline key aspects of Vietnamese belief systems and culture, and consider how these might influence the optimisation of group-based ACT. We then present a mixed-method evaluation of the seven-session adapted ACT group for 11 participants (9 male and 5 female, aged between 44 and 73 years). Individual-level change analyses indicated clinically significant improvements in psychological flexibility for the minority of participants and a mixed pattern for impact on well-being. A thematic analysis and descriptive approach examined acceptability, feasibility and narratives of impact. Participants reported positive feedback on group experience, relevance and usefulness, and emergent themes indicate that the group facilitated key acceptance, commitment and behaviour-change processes, promoted social connections and increased engagement in meaningful life activities in relation to new perspectives and values-based action. Limitations are outlined, but overall, findings suggest preliminary support for the potential beneficial effect of the adapted ACT group as a feasible, culturally acceptable therapeutic approach for UK Vietnamese communities that is worthy of further investigation.

9.
Ann Thorac Surg ; 117(3): 543-549, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37595862

RESUMO

BACKGROUND: Published data on the outcomes of the arterial switch operation in the developing world are limited. We sought to identify the midterm outcomes of and risk factors for mortality and morbidity in patients undergoing the arterial switch operation at a high-volume center in Vietnam. METHODS: A retrospective review was conducted of 608 patients who underwent an arterial switch operation for the treatment of transposition of the great arteries (TGA; n = 509) or double-outlet right ventricle TGA (DORV-TGA; n = 99) at a single center from 2010 to 2021. RESULTS: Overall early mortality was 5.9%, and late mortality was 1%. Multivariate Cox regression showed weight at operation of <3 kg (P < .001), prolonged aortic cross-clamp time (P < .001), and need for secondary aortic cross-clamp (P = .011) as risk factors for overall mortality. The actuarial 10-year survival rate was 93%. The overall cardiac reoperation rate was significantly higher in patients with DORV-TGA (hazard ratio [HR], 16.43; 95% CI, 4.70-57.43; P < .001). The rate of freedom from cardiac reoperation at 10 years was 94%. Risk factors for outflow tract reoperation were patients with DORV-TGA (HR, 23.28; 95% CI, 2.86-189.66; P = .003), single coronary artery (HR, 4.1; 95% CI, 1.16-14.46; P = .028), and mild aortic valve regurgitation observed in 3.7% of patients. CONCLUSIONS: The outcomes of the arterial switch operation in a low- and middle-income country were satisfactory. Nevertheless, the complexity of the procedure and lower weight of patients are still challenges. Patients with DORV-TGA and single coronary artery need to be closely followed up.


Assuntos
Transposição das Grandes Artérias , Dupla Via de Saída do Ventrículo Direito , Transposição dos Grandes Vasos , Humanos , Lactente , Transposição das Grandes Artérias/métodos , Transposição dos Grandes Vasos/cirurgia , Dupla Via de Saída do Ventrículo Direito/cirurgia , Reoperação , Fatores de Risco , Estudos Retrospectivos , Resultado do Tratamento , Seguimentos
10.
Cell Rep ; 43(6): 114333, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38865244

RESUMO

Histone methyltransferases (HMTs) are crucial in gene regulation and function, yet their role in natural killer (NK) cell biology within the tumor microenvironment (TME) remains largely unknown. We demonstrate that the HMT DOT1L limits NK cell conversion to CD49a+ CD49b+ intILC1, a subset that can be observed in the TME in response to stimulation with transforming growth factor (TGF)-ß and is correlated with impaired tumor control. Deleting Dot1l in NKp46-expressing cells reveals its pivotal role in maintaining NK cell phenotype and function. Loss of DOT1L skews NK cells toward intILC1s even in the absence of TGF-ß. Transcriptionally, DOT1L-null NK cells closely resemble intILC1s and ILC1s, correlating with altered NK cell responses and impaired solid tumor control. These findings deepen our understanding of NK cell biology and could inform approaches to prevent NK cell conversion to intILC1s in adoptive NK cell therapies for cancer.


Assuntos
Histona-Lisina N-Metiltransferase , Células Matadoras Naturais , Fenótipo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Animais , Camundongos , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral/imunologia , Camundongos Endogâmicos C57BL , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-37184919

RESUMO

OBJECTIVES: Aortopulmonary window (APW) associated with an interrupted aortic arch (IAA) is a rare cardiac malformation with significant mortality and morbidity. The goal of this study was to report the intermediate outcomes of single-stage repair concentrating on the surgical techniques and postoperative reintervention for this rare cardiac lesion. METHODS: Eleven patients were diagnosed with IAA-associated APW and underwent single-stage surgical repair at Vietnam National Children's Hospital. RESULTS: The APW anatomy types were types I, II and III in 1, 4 and 6 patients, respectively. The IAA morphology was type A in 9 patients and type B in 2 patients. The median age was 27 [interquartile range (IQR) 6-79] days, and the median weight was 3.5 (IQR 2.8-4.5) kg. The aortic arch was repaired using direct end-to-side tissue anastomosis in 7 patients, and patch aortoplasty was performed in 4 patients. Six patients underwent APW closure with an intra-aortic baffle, and 5 patients required right pulmonary artery detachment and reimplantation. One early death occurred. Four patients required reinterventions: 1 patient required reoperation due to aortic stenosis and 3 required balloon angioplasty for either recurrent aortic arch stenosis (n = 1) or right pulmonary stenosis (n = 2) with a mean follow-up time of 3.1 years (IQR 0.5-4.3 years). CONCLUSIONS: Single-stage repair of IAA-associated APW can be achieved with good survival outcomes in children. However, the need for repeat reintervention or reoperation remains high, and the growth of both the aorta and pulmonary arteries should follow carefully as the patient grows. CLINICAL REGISTRATION NUMBER: VNCH-RICH-18-96.

12.
Cancer Cell ; 41(4): 660-677.e7, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-37001527

RESUMO

Pediatric solid and central nervous system tumors are the leading cause of cancer-related death among children. Identifying new targeted therapies necessitates the use of pediatric cancer models that faithfully recapitulate the patient's disease. However, the generation and characterization of pediatric cancer models has significantly lagged behind adult cancers, underscoring the urgent need to develop pediatric-focused cell line resources. Herein, we establish a single-site collection of 261 cell lines, including 224 pediatric cell lines representing 18 distinct extracranial and brain childhood tumor types. We subjected 182 cell lines to multi-omics analyses (DNA sequencing, RNA sequencing, DNA methylation), and in parallel performed pharmacological and genetic CRISPR-Cas9 loss-of-function screens to identify pediatric-specific treatment opportunities and biomarkers. Our work provides insight into specific pathway vulnerabilities in molecularly defined pediatric tumor classes and uncovers biomarker-linked therapeutic opportunities of clinical relevance. Cell line data and resources are provided in an open access portal.


Assuntos
Neoplasias Encefálicas , Criança , Humanos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral
13.
Proc Natl Acad Sci U S A ; 106(36): 15489-94, 2009 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-19706893

RESUMO

The regulation of metal ion transport within neurons is critical for normal brain function. Of particular importance is the regulation of redox metals such as iron (Fe), where excess levels can contribute to oxidative stress and protein aggregation, leading to neuronal death. The divalent metal transporter 1 (DMT1) plays a central role in the regulation of Fe as well as other metals; hence, failure of DMT1 regulation is linked to human brain pathology. However, it remains unclear how DMT1 is regulated in the brain. Here, we show that DMT1 is regulated by Ndfip1 (Nedd4 family-interacting protein 1), an adaptor protein that recruits E3 ligases to ubiquitinate target proteins. Using human neurons we show the Ndfip1 is upregulated and binds to DMT1 in response to Fe and cobalt (Co) exposure. This interaction results in the ubiquitination and degradation of DMT1, resulting in reduced metal entry. Induction of Ndfip1 expression protects neurons from metal toxicity, and removal of Ndfip1 by shRNAi results in hypersensitivity to metals. We identify Nedd4-2 as an E3 ligase recruited by Ndfip1 for the ubiquitination of DMT1 within human neurons. Comparison of brains from Ndfip1(-/-) with Ndfip1(+/+) mice exposed to Fe reveals that Ndfip1(-/-) brains accumulate Fe within neurons. Together, this evidence suggests a critical role for Ndfip1 in regulating metal transport in human neurons.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Cobalto/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Regulação da Expressão Gênica/fisiologia , Ferro/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Western Blotting , Cobalto/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Imunoprecipitação , Transporte de Íons , Ferro/toxicidade , Camundongos , Camundongos Knockout , Ubiquitina-Proteína Ligases Nedd4 , Neurônios/efeitos dos fármacos , Interferência de RNA , Ubiquitinação
14.
Heliyon ; 8(6): e09638, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35677404

RESUMO

This study aims to identify whether demographics, socio-economic factors, the usage of the internet, smartphone and bank, and cultural factor affect Vietnamese adults' financial literacy. A sample of 669 participants participated in the online survey questionnaire (response rate of 89.92%). Multivariate general linear model regression shows that adults of younger age have better skills in cash management, credit management, savings and investment, and financial management compared to older adults. The findings suggest that participants with better income could manage savings and overall finance more effectively. Furthermore, respondents with "Uncertain avoidance" in the culture had better skills in cash management, saving, and investment. Meanwhile, preferring masculinity had higher scores in credit management, insurance, and total scale compared to those preferring femininity. The significant contribution of this study is its usefulness for economic players to have assertive financial strategies and policymakers to enhance the level of financial literacy and provide trustworthy financial guidance.

15.
ACS Omega ; 7(13): 10890-10900, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35415377

RESUMO

We report that the polymerization of cyclodextrin (CD) with epichlorohydrin (ECH) dramatically increases the binding constant of CD to vanillin, from 55 to 8.4 × 103 M-1, by approximately 100 times, as determined by diffusion ordered spectroscopy (DOSY)-1H NMR. The binding constant increased with an increase of the ECH content of the polymer, although ECH polymers without CDs showed no affinity at all, suggesting that the hydrophobicity of the ECH network outside of CDs helps to enhance the binding. This increased binding constant allows CD-ECH polymers to increase the drug loading ratio, which may be one of the most critical issues for drug delivery systems.

16.
J Int AIDS Soc ; 25 Suppl 5: e25996, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36225133

RESUMO

INTRODUCTION: Although HIV prevalence among transgender women who have sex with men in Vietnam is high (16-18%), uptake of pre-exposure prophylaxis (PrEP) is low compared to other populations. When PrEP was initiated in 2017, gender-affirming healthcare was largely unavailable. Lack of access to competent, stigma-free healthcare is a well-documented barrier to transgender women's uptake of PrEP and primary healthcare (PHC). We aimed to demonstrate the utility of a PrEP quality improvement intervention in pinpointing and addressing barriers to PrEP use among transgender women in Vietnam. METHODS: We applied a real-world participatory continuous quality improvement (CQI) and Plan-Do-Study-Act (PDSA) methodology to ascertain barriers to PrEP uptake among transgender women and determine priority actions for quality improvement. A CQI team representing transgender women leaders, key population (KP)-clinic staff, public-sector HIV managers and project staff applied PDSA to test solutions to identified barriers that addressed the primary quality improvement outcome of the monthly change in PrEP uptake among transgender women and secondary outcomes, including month-3 PrEP continuation, the impact of offering PHC on PrEP uptake and unmet PrEP need. We utilized routine programmatic data and a descriptive cross-sectional study enrolling 124 transgender women to measure these outcomes from October 2018 to September 2021. RESULTS: Five key barriers to PrEP uptake among transgender women were identified and corresponding solutions were put in place: (1) offering gender-affirming care training to KP-clinics and community-based organizations; (2) integrating gender-affirming services into 10 KP-clinics; (3) offering PHC through five one-stop shop (OSS) clinics; (4) implementing a campaign addressing concerns related to hormone use and PrEP interactions; and (5) developing national HIV and transgender healthcare guidelines. New PrEP enrolment and month-3 PrEP continuation increased significantly among transgender women. Of 235 transgender women who initially sought healthcare other than PrEP at OSS clinics, 26.4% subsequently enrolled in PrEP. About one-third of transgender women reported unmet PrEP need, while two-thirds indicated an interest in long-acting cabotegravir. CONCLUSIONS: Offering gender-competent, integrated PHC can increase PrEP enrolment and continuation, and can be an entry-point for PrEP among those seeking care within PHC clinics. More work is needed to expand access to transgender women-led and -competent healthcare in Vietnam.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Pessoas Transgênero , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Hormônios , Humanos , Masculino , Profilaxia Pré-Exposição/métodos , Atenção Primária à Saúde , Vietnã
17.
Sci Adv ; 7(21)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34138730

RESUMO

Aberrant activation of Wnt/ß-catenin pathway is a key driver of colorectal cancer (CRC) growth and of great therapeutic importance. In this study, we performed comprehensive CRISPR screens to interrogate the regulatory network of Wnt/ß-catenin signaling in CRC cells. We found marked discrepancies between the artificial TOP reporter activity and ß-catenin-mediated endogenous transcription and redundant roles of T cell factor/lymphoid enhancer factor transcription factors in transducing ß-catenin signaling. Compiled functional genomic screens and network analysis revealed unique epigenetic regulators of ß-catenin transcriptional output, including the histone lysine methyltransferase 2A oncoprotein (KMT2A/Mll1). Using an integrative epigenomic and transcriptional profiling approach, we show that KMT2A loss diminishes the binding of ß-catenin to consensus DNA motifs and the transcription of ß-catenin targets in CRC. These results suggest that KMT2A may be a promising target for CRCs and highlight the broader potential for exploiting epigenetic modulation as a therapeutic strategy for ß-catenin-driven malignancies.


Assuntos
Neoplasias Colorretais , beta Catenina , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição TCF/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
18.
Adv Sci (Weinh) ; 6(20): 1900579, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31637158

RESUMO

Merging photonic structures and optoelectronic sensors into a single chip may yield a sensor-on-chip spectroscopic device that can measure the spectrum of matter. In this work, an on-chip concurrent multiwavelength infrared (IR) sensor, which consists of a set of narrowband wavelength-selective plasmonic perfect absorbers combined with pyroelectric sensors, where the response of each pyroelectric sensor is boosted only at the resonance of the nanostructured absorber, is proposed and realized. The proposed absorber, which is based on Wood's anomaly absorption from a 2D plasmonic square lattice, shows a narrowband polarization-independent resonance (quality factor - Q of 73) with a nearly perfect absorptivity as high as 0.99 at normal incidence. The fabricated quad-wavelength IR sensors exhibit four different narrowband spectral responses at normal incidence following the predesigned resonances in the mid-wavelength infrared region that corresponds to the atmospheric window. The device can be applied for practical spectroscopic applications such as nondispersive IR sensors, IR chemical imaging devices, pyrometers, and spectroscopic thermography imaging.

19.
Micromachines (Basel) ; 10(6)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234295

RESUMO

Spectrally selective detection is of crucial importance for diverse modern spectroscopic applications such as multi-wavelength pyrometry, non-dispersive infrared gas sensing, biomedical analysis, flame detection, and thermal imaging. This paper reports a quad-wavelength hybrid plasmonic-pyroelectric detector that exhibited spectrally selective infrared detection at four wavelengths-3.3, 3.7, 4.1, and 4.5 µm. The narrowband detection was achieved by coupling the incident infrared light to the resonant modes of the four different plasmonic perfect absorbers based on Al-disk-array placed on a Al2O3-Al bilayer. These absorbers were directly integrated on top of a zinc oxide thin film functioning as a pyroelectric transducer. The device was fabricated using micro-electromechanical system (MEMS) technology to optimize the spectral responsivity. The proposed detector operated at room temperature and exhibited a responsivity of approximately 100-140 mV/W with a full width at half maximum of about 0.9-1.2 µm. The wavelength tunability, high spectral resolution, compactness and robust MEMS-based platform of the hybrid device demonstrated a great advantage over conventional photodetectors with bandpass filters, and exhibited impressive possibilities for miniature multi-wavelength spectroscopic devices.

20.
Micromachines (Basel) ; 11(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878232

RESUMO

Among conductive oxide materials, niobium doped titanium dioxide has recently emerged as a stimulating and promising contestant for numerous applications. With carrier concentration tunability, high thermal stability, mechanical and environmental robustness, this is a material-of-choice for infrared plasmonics, which can substitute indium tin oxide (ITO). In this report, to illustrate great advantages of this material, we describe successful fabrication and characterization of niobium doped titanium oxide nanoantenna arrays aiming at surface-enhanced infrared absorption spectroscopy. The niobium doped titanium oxide film was deposited with co-sputtering method. Then the nanopatterned arrays were prepared by electron beam lithography combined with plasma etching and oxygen plasma ashing processes. The relative transmittance of the nanostrip and nanodisk antenna arrays was evaluated with Fourier transform infrared spectroscopy. Polarization dependence of surface plasmon resonances on incident light was examined confirming good agreements with calculations. Simulated spectra also present red-shift as length, width or diameter of the nanostructures increase, as predicted by classical antenna theory.

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