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1.
J Infect Dis ; 230(3): 689-695, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-38700101

RESUMO

We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV preexposure prophylaxis during pregnancy and postpartum and compared hair levels with TFV-diphosphate levels in dried blood spots (DBSs). Overall 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster-randomized trial. Having a partner with HIV was associated with higher hair TFV levels (P < .001). Hair TFV concentrations were strongly correlated with DBS TFV-diphosphate levels (r = 0.76, P < .001), indicating hair as a promising cumulative adherence metric for perinatal preexposure prophylaxis assessment.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Cabelo , Período Pós-Parto , Profilaxia Pré-Exposição , Tenofovir , Humanos , Feminino , Gravidez , Cabelo/química , Infecções por HIV/prevenção & controle , Adulto , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/sangue , Tenofovir/uso terapêutico , Teste em Amostras de Sangue Seco/métodos , Adesão à Medicação/estatística & dados numéricos , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto Jovem , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/administração & dosagem , Adenina/farmacocinética , Adenina/sangue , Organofosfatos
2.
Curr HIV/AIDS Rep ; 21(5): 264-281, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39120667

RESUMO

PURPOSE OF REVIEW: Adherence-concentration-efficacy benchmarks have not been fully characterized for cisgender women using emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) oral daily pre-exposure prophylaxis (PrEP) for HIV prevention. RECENT FINDINGS: We conducted a systematic review to investigate current evidence on the adherence-concentration-efficacy relationship of tenofovir-diphosphate (TFV-DP) derived from FTC/TDF PrEP in dried blood spots (DBS) and peripheral mononuclear cells (PBMC) in cisgender women without HIV, including during pregnancy. We searched for completed and ongoing studies published before May 2024 in PubMed, Embase, Cochrane Library, CINAHL, and clinicaltrial.gov.  Overall, 11 studies assessing adherence benchmarks focusing on (n = 5) or involving (n = 6) cisgender women were included. Women-specific median steady-state TFV-DP concentration for daily dosing ranged from 17 to 51 fmol/106 in PBMC and 1389 to 1685 fmol/punch in DBS in non-pregnant women; 50 to 71 fmol/106 in PBMC and 583 to 965 fmol/punch in DBS in pregnant women; and 618 to 1406 fmol/punch in DBS in postpartum women. DBS TFV-DP levels were 14-43% lower in pregnancy versus postpartum or non-pregnant periods, but PBMC TFV-DP levels appear to be comparable. Clinical and modeling studies demonstrate effective HIV protection for women taking at least four doses/week of oral TDF-based PrEP, and emerging evidence suggests that systemic drug levels are more likely to be predictive of efficacy than local tissue levels at the site of exposure. The preponderance of emerging evidence points to comparable efficacy and similar adherence requirement for women as men among those with detectable drug levels, although there was an indication that the highest achievable efficacy may be reached at a lower adherence level in men than women. In this review, we found evidence that women-specific TFV-DP adherence benchmarks in DBS and PBMC are within range of US-based historical thresholds derived from healthy men and women. Emerging evidence suggests that imperfect but adequate adherence to oral FTC/TDF PrEP with at least four doses/week provides sufficient HIV protection in cisgender women as it does in MSM, but more data are still needed to refine intrinsic achievable efficacy estimates for cisgender women.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Profilaxia Pré-Exposição , Tenofovir , Humanos , Profilaxia Pré-Exposição/métodos , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Gravidez , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Leucócitos Mononucleares , Adenina/análogos & derivados , Organofosfatos
3.
J Nanobiotechnology ; 22(1): 366, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918821

RESUMO

Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management.


Assuntos
Neoplasias da Mama , Humanos , Neoplasias da Mama/terapia , Feminino , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Animais , Fotoquimioterapia/métodos , Compostos Inorgânicos/química
4.
Int J Mol Sci ; 24(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37047628

RESUMO

Although several regulators associated with purple traits in rice have been identified, the genetic basis of the purple sheath remains unclear. In the present study, F2-1 and F2-2 populations were constructed using purple sheath (H93S) and green sheath (R1173 and YHSM), respectively. In order to identify QTL loci in purple sheaths, BSA analyses were performed on the two F2 populations. A crucial QTL for purple sheath was identified, tentatively named qPLSr6, and was located in the 4.61 Mb to 6.03 Mb region of chromosome 6. Combined with expression pattern analysis of candidate genes, LOC_Os06g10350 (OsC1PLSr) was suggested as a candidate gene. The homozygous mutant KO-1 and KO-2 created through CRISPR/Cas9 editing, lost their purple leaf sheath. The RT-PCR revealed that OsC1PLSr, anthocyanin synthase (ANS), diflavonol-4-reductase (DFR), flavanone-3-hydroxylase (F3H), and flavanone-3'-hydroxylase (F3'H) expression levels were dramatically down-regulated in the mutants. The yeast report system indicated that the 145-272 aa region at the C-terminal of OsC1PLSr is a positive transcriptional activation domain. The results indicated that OsC1PLSr synthesized anthocyanins by regulating the expression of ANS, DFR, F3H, and F3'H. This study provides new insights into the genetic basis of the purple sheath.


Assuntos
Flavanonas , Oryza , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Antocianinas/metabolismo , Oryza/genética , Oryza/metabolismo , Regulação da Expressão Gênica de Plantas , Folhas de Planta/genética , Folhas de Planta/metabolismo , Oxirredutases/metabolismo , Oxigenases de Função Mista/genética , Flavanonas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
Environ Monit Assess ; 195(12): 1427, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938459

RESUMO

The shrub encroachment caused by Caragana species (mainly C. microphylla, C. korshinskii, C. tibetica, C. stenophylla, and C. pygmaea) in the north temperate zone has significant impacts on ecosystems. Understanding the distribution of Caragana species' responses to climate change is increasingly relevant to the dynamic of shrub encroachment. In this study, we gathered 1124 geographical distribution records for 5 Caragana species. Through principal component analysis and Pearson correlation analysis, 11 environmental variables were identified. We employed the maximum entropy (MaxEnt) model and utilized the current and future climate dataset from 2041 to 2060 based on two extreme climate scenarios (RCP2.6 and RCP8.5) and atmospheric circulation models (BCC_CSM1.1 and IPSLCM5A-LR) to assess the potential distribution patterns and dynamic change with global warming. The results showed the following: (1) Currently, the five Caragana species are mainly distributed in the central and western parts of the Inner Mongolia Autonomous Region, Mongolia, and the southern parts of Russia. (2) In the future, the habitable zone of C. microphylla and C. korshinskii will expand gradually, while the distribution probability of C. stenophylla, C. tibetica, and C. pygmaea will shrink significantly in 60-80% of the area, and the habitable area will fluctuate sharply. (3) The range of the five species of Caragana expansion area is projected to be 1229.43×106 km2-1412.32×106 km2, with the suitable habitats expected to extend northward in the future, primarily concentrated in central Mongolia and around Lake Baikal in Russia. This research provides guidance for protecting grassland resources and ensuring sustainable development under shrub encroachment.


Assuntos
Caragana , Ecossistema , Monitoramento Ambiental , Simulação por Computador , China
6.
Matern Child Health J ; 26(1): 139-148, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34845572

RESUMO

OBJECTIVES: To characterize contraceptive method use and satisfaction among Spanish-speaking Latina immigrants who attend their child's well care visit. METHODS: Spanish-speaking women whose youngest child was ≤ 4 years old completed an orally-administered Spanish-language survey in a pediatric clinic (N = 194). Survey items were based on previously published contraceptive use assessments among diverse populations. We used chi-square and Fisher exact test to describe maternal characteristics by contraceptive method effectiveness categories: Tier 1, most effective methods (hormonal implant, intrauterine device, tubal ligation, and vasectomy); Tier 2, very effective methods (hormonal injection, oral contraceptive pill, hormonal patch, and hormonal ring); Tier 3, effective methods (condoms), and no method. RESULTS: 34% of women were using a Tier 1 method, 40% were using a Tier 2 method, and 17% had unmet contraceptive need (no pregnancy intention, no birth control); 84% were satisfied with their current method and 82% of women were uninsured. Tier 2 method or no method users were more likely than women using a Tier 1 method to have children < 9 months old (X2 (6, N = 190) = 20.4, p = .002). CONCLUSIONS: Latina immigrants with young children who attend their child's pediatric visit are mostly using effective contraceptives and are satisfied with their method. A culturally supportive medical home and access to no-cost long-acting reversible contraceptives through a temporary private grant likely contributed to high contraceptive use and satisfaction in our study. Describing maternal contraceptive use among Latina immigrant mothers can inform future equitable, culturally tailored, approaches to pediatric maternal contraceptive need screening.


Assuntos
Anticoncepcionais , Mães , Criança , Pré-Escolar , Anticoncepção , Feminino , Hispânico ou Latino , Humanos , Lactente , Idioma
7.
Int J Mol Sci ; 23(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36498964

RESUMO

The loss of the shattering ability is one of the key events in rice domestication. The strength of the seed shattering ability is closely related to the harvest yield and the adaptability of modern mechanical harvesting methods. In this study, using a population of 587 natural rice cultivars, quantitative trait loci associated with seed shattering were detected by genome-wide association studies (GWASs). We consider the quantitative trait loci (QTLs) qBTS1 and qBTS3 to be the key loci for seed shattering in rice. Additionally, the abscission zone (AZ) and nonabscission zone (NAZ) of materials with a loss of shattering (DZ129) and easy shattering (W517) were subjected to RNA-Seq, and high-quality differential expression profiles were obtained. The AZ-specific differentially expressed genes (DEGs) of W517 were significantly enriched in plant hormone signal transduction, while the AZ-specific DEGs of DZ129 were enriched in phenylpropanoid biosynthesis. We identified candidate genes for the lignin-associated laccase precursor protein (LOC_Os01g63180) and the glycoside hydrolase family (LOC_Os03g14210) in the QTLs qBTS1 (chromosome 1) and qBTS3 (chromosome 3), respectively. In summary, our findings lay the foundation for the further cloning of qBTS1 and qBTS3, which would provide new insights into seed shattering in rice.


Assuntos
Oryza , Oryza/genética , Estudo de Associação Genômica Ampla , RNA-Seq , Fenótipo , Sementes/genética
8.
Matern Child Health J ; 25(12): 1807-1813, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34687401

RESUMO

INTRODUCTION: Development of mHealth interventions to address health disparities for Latino children in immigrant families requires understanding access to and use of information and communication technology. METHODS: We examined access to information and communication technology and use of common applications/programs by low-income immigrant Latino parents of infants to inform development of mHealth interventions for this population. Latino immigrant parents reported technology use and access of common applications/software via survey. RESULTS: Of the 157 participants, we found nearly all parents owned a smartphone and that 60% accessed the internet only via their smartphone. Around one-quarter of participants had access to unlimited data. Frequent use of text messaging was common, but frequent email use was less common. Less than 10% of participants frequently used health-oriented applications. DISCUSSION: Our findings suggest that mHealth interventions that use data, email, or an application interface may not have the intended reach or effectiveness among low-income immigrant Latino parents. Consideration of these findings is important in guiding the development of future mHealth programs for the low-income Latino population. This study was registered at clinicaltrials.gov (NCT02647814).


Assuntos
Emigrantes e Imigrantes , Telemedicina , Acesso à Informação , Hispânico ou Latino , Humanos , Pais , Tecnologia
9.
Clin Infect Dis ; 71(10): 2637-2644, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31761944

RESUMO

BACKGROUND: Human immunodeficiency virus pre-exposure prophylaxis (PrEP) clinical guidelines recommend men who have sex with men (MSM) PrEP users be screened biannually for syphilis and gonorrhea/chlamydia at all anatomic sites. We sought to determine the proportion screened and positive by STI and anatomic site at PrEP initiation and PrEP-care visits and patient-level characteristics associated with screening among MSM PrEP users in Baltimore City, Maryland. METHODS: Medical records among MSM initiating PrEP between 30 September 2015 and 31 March 2018 were abstracted. STI screening (syphilis and gonorrhea/chlamydia at all anatomic sites) and positivity at PrEP visits ≤12 months following initiation were calculated. Poisson regression with cluster robust SEs was used to assess associations with STI screening. RESULTS: Among 290 MSM initiating PrEP, 43.1% (n = 125) were screened per guidelines at PrEP initiation; 79.3% (230), 69.3% (201), 55.9% (162), and 69.3% (201) were screened for syphilis, urogenital, rectal, and oropharyngeal gonorrhea/chlamydia, respectively. Positivity among those screened was syphilis, 7.8% (n = 18/230); gonorrhea, 5.0% urogenital (10/201), 11.1% rectal (18/162), and 7.5% oropharyngeal (15/201); chlamydia, 5.0% urogenital (10/201), 11.7% rectal (19/162), and 1.5% oropharyngeal (3/201). Reported anal and oral sex (vs neither) was independently associated with STI screening (aPR, 2.11; 1.05-4.27) at PrEP initiation. At biannual PrEP-care visits, STI screening was lower and syphilis and rectal gonorrhea/chlamydia positivity was higher. CONCLUSIONS: Observed STI screening levels and disease burden suggest the effectiveness of STI screening in PrEP care for STI prevention may be limited. Our results suggest providers may be offering screening based on sexual practices; clarification of STI screening guidelines for PrEP users is needed.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Baltimore/epidemiologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/prevenção & controle , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Gonorreia/prevenção & controle , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle
10.
Lab Invest ; 94(7): 777-87, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24840331

RESUMO

The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication.


Assuntos
Infecções por HIV/fisiopatologia , HIV-1/metabolismo , Doenças Retinianas/fisiopatologia , Epitélio Pigmentado da Retina/fisiopatologia , Translocação Bacteriana , Western Blotting , Linhagem Celular , Quimiocina CCL2/metabolismo , Células Epiteliais/metabolismo , Escherichia coli/metabolismo , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/metabolismo , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Interleucina-6/metabolismo , Microscopia de Fluorescência , Mutação , Permeabilidade , Doenças Retinianas/metabolismo , Doenças Retinianas/virologia , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/virologia , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/fisiologia
11.
Gen Thorac Cardiovasc Surg ; 72(7): 480-486, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38231367

RESUMO

BACKGROUND: The manubrium and body of the sternum are connected by the manubrium-sternum joint (MSJ). In performing the Nuss procedure for pectus excavatum patients, the body of the sternum is elevated as the operator flips correction bars upside down. Theoretically, the presence of the MSJ should allow elevation of the sternum body. However, does the MSJ secure sufficient elevation of the sternum? This study aims to elucidate this clinical question. METHODS: Seventy-four adult pectus excavatum patients with moderate to serious deformity (with Haller Index being equal to or greater than 5) were included in the study. The MSJ was open in all patients. For 29 patients, the sternum was elevated by only bar flipping (Non-Separation Group); for 45 patients, the sternum was horizontally separated after bar flipping (Separation Group). Whether or not additional elevation for Separation Group patients results from the division was observed, and the degree of the additional elevation was evaluated. Furthermore, 74 patients subjectively evaluated postoperative pain and gave scores with a Visual Analog Scale ranging from 0 (no pain) to 10 (intolerable pain). The VAS scores were compared between the two groups. RESULTS: In the Separation Group, the sternums of all patients achieved additional elevation from sternum separation. The pain scores were lower for the Separation Group than for the Non-Separation Group. CONCLUSION: Even when the MSJ is present, horizontal separation enhances the elevation of the sternum. Furthermore, horizontal separation of the sternum reduces postoperative pain.


Assuntos
Tórax em Funil , Manúbrio , Esterno , Humanos , Tórax em Funil/cirurgia , Esterno/cirurgia , Masculino , Feminino , Manúbrio/cirurgia , Adulto , Adulto Jovem , Resultado do Tratamento , Adolescente , Dor Pós-Operatória/etiologia , Procedimentos Ortopédicos/métodos , Procedimentos Ortopédicos/efeitos adversos , Medição da Dor
12.
Lancet HIV ; 11(11): e765-e773, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39312933

RESUMO

BACKGROUND: Injectable lenacapavir administered every 6 months is a promising product for HIV pre-exposure prophylaxis (PrEP). We aimed to estimate the health and budget impacts and threshold price at which lenacapavir could be cost-effective in eastern and southern Africa. METHODS: We adapted an agent-based network model, EMOD-HIV, to simulate lenacapavir scale-up in Zimbabwe, South Africa, and western Kenya from 2026 to 2035. Uptake assumptions were informed by a literature review of PrEP product preferences. In the main analysis, we varied lenacapavir coverage by subgroup: female sex workers (40% coverage); male clients of female sex workers (40%); adolescent girls and young women aged 15-24 years with more than one sexual partner (32%); women aged 25 years and older with more than one sexual partner (36%); and males with more than one sexual partner (32%). We also assessed a higher coverage scenario (64-76% across subgroups) and scenarios of expanding lenacapavir use, varying from concentrated among those at highest HIV risk to broader coverage including those at medium HIV risk. We estimated the maximum per-dose lenacapavir price that achieved cost-effectiveness (

Assuntos
Fármacos Anti-HIV , Análise Custo-Benefício , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/economia , Profilaxia Pré-Exposição/economia , Profilaxia Pré-Exposição/métodos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Fármacos Anti-HIV/economia , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Orçamentos , África Austral/epidemiologia , África Oriental/epidemiologia , Profissionais do Sexo
13.
Food Chem X ; 21: 101203, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38384683

RESUMO

The study characterized the aroma-active compounds produced by sesame hulls at three roasting temperatures and analyzed the similarities and differences in the aroma profile of sesame hulls with whole seeds and kernels after roasting. Roasting hulls produced mainly furans, aldehydes, and ketones volatiles. 140 Compounds were identified as aroma-active compounds, including 36 key aroma compounds (odor activity value, OAV ≥ 1). Among them, furanone (caramel-like, OAV = 80), 3-methylbutanal (fruity, OAV = 124), and 2-methoxy-4-vinylphenol (burnt, smoky, OAV = 160) gave hulls (180 °C) sweet, burnt, and smoky aroma. Due to the contribution of vanillin (fatty, sweet milk, OAV = 45), 2-hydroxy-3-butanone (caramel-like, roast, OAV = 46), and 2-methoxy-4-vinylphenol (OAV = 78), hulls (200 °C) shown strong sweet and roast note. These results identified compounds that contributed significantly to the aroma of sesame hulls and elucidated the contribution of sesame hulls to the flavor of roasted whole seeds and sesame oil.

14.
Front Reprod Health ; 6: 1325257, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860025

RESUMO

Background: Oral pre-exposure prophylaxis (PrEP) using co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) is a potent HIV prevention method for men and women, with its efficacy highly dependent on adherence. A pivotal HIV efficacy study combined with a directly observed pharmacological study defined the thresholds for HIV protection in men who have sex with men (MSM), which are the keys to PrEP promotion and development of new PrEP agents. For African women at risk for HIV and belonging to a priority group considered due to disproportionately high incident HIV infections, the variable adherence in PrEP clinical trials and the limited pharmacologic data have resulted in a lack of clarity about the PrEP adherence required for HIV protection. We propose a study to quantify the adherence-concentration-efficacy thresholds of TDF/FTC PrEP among African cisgender women to inform decisions about optimal PrEP dosing and adherence for HIV protection. Methods: We randomized 45 low-risk HIV-uninfected African women, aged 18-30 years old, to directly observe the TDF/FTC PrEP of two, four, or seven doses per week for 8 weeks. A complementary age-matched pregnant women cohort at high risk of HIV, who will receive seven doses per week, was recruited (N = 15) with the primary aim of establishing benchmark concentrations in dried blood spots and peripheral blood mononuclear cells. Plasma, whole blood (WB), urine, hair, vaginal fluid, and vaginal tissue (non-pregnant women only) were archived for future testing. Drug concentrations were measured using methods validated for each biological matrix. Pharmacokinetic models were fitted to drug concentrations to quantify concentration-adherence thresholds. To define the drug concentrations associated with HIV protection, we applied the newly defined thresholds from the primary pharmacologic trial to the subset of women randomized to TDF/FTC or TDF in the Partners PrEP Study with the drug concentration assessed in plasma and WB samples. Multiple imputation was used to construct a data set with drug concentrations at each visit when an HIV test was performed for the entire cohort, replicating the work for MSM. Discussion: The proposed study generated the first African women-specific TDF-PrEP adherence-concentration-efficacy thresholds essential for guiding the accurate interpretation of TDF/FTC PrEP programs and clinical trials of novel HIV prevention products using TDF/FTC as an active control. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT05057858).

15.
Lancet HIV ; 11(3): e167-e175, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301668

RESUMO

BACKGROUND: Community-based oral pre-exposure prophylaxis (PrEP) provision has the potential to expand PrEP coverage. HIV self-testing can facilitate PrEP community-based delivery but might have lower sensitivity than facility-based HIV testing, potentially leading to inappropriate PrEP use among people with HIV and subsequent development of drug resistance. We aimed to evaluate the impact of HIV self-testing use for PrEP scale-up. METHODS: We parameterised an agent-based network model, EMOD-HIV, to simulate generic tenofovir disoproxil fumarate and emtricitabine PrEP scale-up in western Kenya using four testing scenarios: provider-administered nucleic acid testing, provider-administered rapid diagnostic tests detecting antibodies, blood-based HIV self-testing, or oral fluid HIV self-testing. Scenarios were compared with a no PrEP counterfactual. Individuals aged 18-49 years with one or more heterosexual partners who screened HIV-negative were eligible for PrEP. We assessed the cost and health impact of rapid PrEP scale-up with high coverage over 20 years, and the budget impact over 5 years, using various HIV testing modalities. FINDINGS: PrEP coverage of 29% was projected to avert approximately 54% of HIV infections and 17% of HIV-related deaths among adults aged 18-49 years over 20 years; health impacts were similar across HIV testing modalities used to deliver PrEP. The percentage of HIV infections with PrEP-associated nucleoside reverse transcriptase inhibitor (NRTI) drug resistance was 0·6% (95% uncertainty intervals 0·4-0·9) in the blood HIV self-testing scenario and 0·8% (0·6-1·0) in the oral HIV self-testing scenario, compared with 0·3% (0·2-0·3) in the antibody rapid diagnostic testing scenario and 0·2% (0·1-0·2) in the nucleic acid testing scenario. Accounting for background NRTI resistance, we found similarly low proportions of drug resistance across scenarios. The budget impact of implementing PrEP using HIV self-testing and provider-administered rapid diagnostic tests were similar, while nucleic acid testing was approximately 50% more costly. INTERPRETATION: Scaling up PrEP using HIV self-testing has similar health impacts, costs, and low risk of drug resistance as provider-administered rapid diagnostic tests. Policy makers should consider leveraging HIV self-testing to expand PrEP access among those at HIV risk. FUNDING: The Bill and Melinda Gates Foundation.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Ácidos Nucleicos , Profilaxia Pré-Exposição , Adulto , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Quênia/epidemiologia , Autoteste , Emtricitabina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Teste de HIV , Ácidos Nucleicos/uso terapêutico
16.
Front Reprod Health ; 5: 944372, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457431

RESUMO

Background: Persons living in sub-Saharan Africa (SSA) face disproportionate risk from overlapping epidemics of HIV and bacterial sexually transmitted infections (STIs). Pre-exposure prophylaxis (PrEP) for prevention is gradually being scaled up globally including in several settings in SSA, which represents a key opportunity to integrate STI services with HIV pre-exposure prophylaxis (PrEP). However, there is limited literature on how to successfully integrate these services, particularly in the SSA context. Prior studies and reviews on STI and PrEP services have largely focused on high income countries. Methods: We conducted a scoping review of prior studies of integration of STI and PrEP services in SSA. We searched PubMed, EMBASE, Cochrane, and CINAHL, in addition to grey literature to identify studies that were published between January 2012 and December 2022, and which provided STI and PrEP services in SSA, with or without outcomes reported. Citations and abstracts were reviewed by two reviewers for inclusion. Full texts were then retrieved and reviewed in full by two reviewers. Results: Our search strategy yielded 1951 records, of which 250 were retrieved in full. Our final review included 61 reports of 45 studies. Most studies were conducted in Southern (49.2%) and Eastern (24.6%) Africa. Service settings included public health clinics (26.2%), study clinics (23.0%), sexual and reproductive care settings (23.0%), maternal and child health settings (8.2%), community based services (11.5%), and mobile clinics (3.3%). A minority (11.4%) of the studies described only syndromic STI management while most (88.6%) included some form of etiological laboratory STI diagnosis. STI testing frequency ranged from baseline testing only to monthly screening. Types of STI tested for was also variable. Few studies reported outcomes related to implementation of STI services. There were high rates of curable STIs detected by laboratory testing (baseline genitourinary STI rates ranged from 5.6-30.8% for CT, 0.0-11.2% for GC, and 0.4-8.0% for TV). Discussion: Existing studies have implemented a varied range of STI services along with PrEP. This range reflects the lack of specific guidance regarding STI services within PrEP programs. However, there was limited evidence regarding implementation strategies for integration of STI and PrEP services in real world settings.

17.
Eplasty ; 23: e65, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38045098

RESUMO

Background: Severing part of the thorax prior to bar placement is effective to improve outcomes in performing the Nuss procedure for asymmetric pectus excavatum. This study aims to elucidate the patterns of severing to provide an ideal outcome. Methods: Three-dimensional biomechanical computer models were produced simulating the thoraxes of 10 actual patients with asymmetric pectus excavatum. Virtual surgical operation was performed on the 10 models in 4 patterns: group 1-no part of the thorax was severed (default group). Group 2-The sternum was severed (sternum-severing group). Group 3-The ribs on the affected side were severed (rib-severing group). Group 4-Both the sternum and ribs on the affected side were severed (sternum/rib-severing group). After performing this preparation, simulation of bar placement was performed. Comparing the pre- and postoperative shapes of the models, we examined whether symmetry improved for each group. Results: Symmetry of the chest wall improved for rib-severing group and sternum/rib-severing group. Asymmetry remained for default group and sternum-severing group. Conclusions: Performance of the Nuss procedure for asymmetric pectus excavatum does not greatly improve symmetry of the chest wall. Severing the ribs as an additional maneuver is effective to improve symmetry.

18.
Mater Today Bio ; 20: 100673, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37441136

RESUMO

Glioma is one of the most serious central nervous system diseases, with high mortality and poor prognosis. Despite the continuous development of existing treatment methods, the median survival time of glioma patients is still only 15 months. The main treatment difficulties are the invasive growth of glioma and the obstruction of the blood-brain barrier (BBB) to drugs. With rapid advancements in nanotechnology, inorganic nanoparticles (INPs) have shown favourable application prospects in the diagnosis and treatment of glioma. Due to their extraordinary intrinsic features, INPs can be easily fabricated, while doping with other elements and surface modification by biological ligands can be used to enhance BBB penetration, targeted delivery and biocompatibility. Guided glioma theranostics with INPs can improve and enhance the efficacy of traditional methods such as chemotherapy, radiotherapy and gene therapy. New strategies, such as immunotherapy, photothermal and photodynamic therapy, magnetic hyperthermia therapy, and multifunctional inorganic nanoplatforms, have also been facilitated by INPs. This review emphasizes the current state of research and clinical applications of INPs, including glioma targeting and BBB penetration enhancement methods, in vivo and in vitro biocompatibility, and diagnostic and treatment strategies. As such, it provides insights for the development of novel glioma treatment strategies.

19.
Biology (Basel) ; 12(11)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37997964

RESUMO

Tetrabromobisphenol A (TBBPA), a commonly utilized brominated flame retardant, is found in many types of abiotic and biotic matrices. TBBPA can increase oxidative stress, disrupt the endocrine system, cause neurodevelopmental disorders and activate peroxisome proliferator-activated receptors to modulate lipid deposits in aquatic animals. However, the toxic mechanism of TBBPA on the gut microbiota and intestinal health remains unclear. Apostichopus japonicus is an ideal model for studying the relationship between environmental contaminants and intestinal health due to its unique capacity for evisceration and quickly regenerated intestine. In the present study, we investigated the toxic mechanism of TBBPA on the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. The results show that TBBPA exposure decreased the health of the regenerated intestine and the enzymatic activities, alpha diversity indices, and the relative abundance of the gut microbiota. Transcriptome analysis shows that TBBPA exposure affected lipid metabolism via the PPAR signaling pathway during the process of intestinal regeneration in A. japonicus, suggesting that TBBPA exposure can affect the composition and function of the gut microbiota and intestinal health in the regenerated intestine of A. japonicus. These results provide a basis for further research on the potential toxicity of TBBPA to the intestinal health in animals.

20.
Sci Rep ; 13(1): 6707, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37185291

RESUMO

Mutation breeding is a significant means of increasing breeding efficiency and accelerating breeding process. In present study, we explored a new method for mutations inducing in rice (Oryza sativa L.) by using direct current electrophoresis bath (DCEB). The results showed that 20 mM NaCl solution is the optimal buffer, and the mortality of rice seeds followed an upward trend with increasing voltage and processing time of DCEB. By exploring the mutagenic effects of γ-irradiation and DCEB on seed vigor and physiological damages, we found that the physiological damages induced by DCEB on seed vigor were significant compared with that by γ-irradiation. We screened two mutants with low filled grain percentage and one mutant with abnormal hull from the M2 generations. These three mutants were confirmed to be authentic mutants based on 48 SSR markers followed by the protocol NY/T 1433-2014. Whole-genome resequencing detected a total of 503 and 537 polymorphisms in the two mutants, respectively, and the DCEB mutagenesis induced mainly InDel variants, while the exon region of mutant genes occupied a large proportion, especially the SNP variants, which occupied about 20% of the mutation sites in the exon region.


Assuntos
Oryza , Oryza/genética , Oryza/efeitos da radiação , Mutagênicos , Melhoramento Vegetal , Mutação , Mutagênese/genética , Sementes/genética
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