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1.
Brief Funct Genomics ; 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38944027

ABSTRACT

Acute myeloid leukemia (AML) is a type of blood cancer with diverse genetic variations and DNA methylation alterations. By studying the interaction of gene mutations, expression, and DNA methylation, we aimed to gain valuable insights into the processes that lead to block differentiation in AML. We analyzed TCGA-LAML data (173 samples) with RNA sequencing and DNA methylation arrays, comparing FLT3 mutant (48) and wild-type (125) cases. We conducted differential gene expression analysis using cBioPortal, identified DNA methylation differences with ChAMP tool, and correlated them with gene expression changes. Gene set enrichment analysis (g:Profiler) revealed significant biological processes and pathways. ShinyGo and GeneCards were used to find potential transcription factors and their binding sites among significant genes. We found significant differentially expressed genes (DEGs) negatively correlated with their most significant methylation probes (Pearson correlation coefficient of -0.49, P-value <0.001) between FLT3 mutant and wild-type groups. Moreover, our exploration of 450 k CpG sites uncovered a global hypo-methylated status in 168 DEGs. Notably, these methylation changes were enriched in the promoter regions of Homebox superfamily gene, which are crucial in transcriptional-regulating pathways in blood cancer. Furthermore, in FLT3 mutant AML patient samples, we observed overexpress of WT1, a transcription factor known to bind homeobox gene family. This finding suggests a potential mechanism by which WT1 recruits TET2 to demethylate specific genomic regions. Integrating gene expression and DNA methylation analyses shed light on the impact of FLT3 mutations on cancer cell development and differentiation, supporting a two-hit model in AML. This research advances understanding of AML and fosters targeted therapeutic strategy development.

2.
Article in English | MEDLINE | ID: mdl-38397665

ABSTRACT

Foods and beverages high in free sugars can displace healthier choices and increase the risk of weight gain, dental caries, and noncommunicable diseases. Little is known about the intake of free sugars across early childhood. This study aimed to examine the longitudinal intake from 1 to 5 years of free sugars and identify the independent maternal and child-related predictors of intake in a cohort of Australian children participating in the Study of Mothers' and Infants' Life Events Affecting Oral Health (SMILE). Free sugars intake (FSI) was previously estimated at 1, 2, and 5 years of age, and three distinct FSI trajectories were determined using group-based trajectory modelling analysis. This study utilized multinomial logistic regression to identify the maternal and child-related predictors of the trajectories. The risk of following the 'high and increasing' trajectory of FSI compared to the 'low and fast increasing' trajectory was inversely associated with socio-economic disadvantage (aRRR 0.83; 95% CI 0.75-0.92; p < 0.001), lower for females (aRRR 0.56; 95% CI 0.32-0.98; p = 0.042), and higher in children with two or more older siblings at birth (aRRR 2.32; 95% CI 0.99-5.42; p = 0.052). Differences in trajectories of FSI were evident from an early age and a high trajectory of FSI was associated primarily with socio-economic disadvantage, providing another example of diet quality following a social gradient.


Subject(s)
Dental Caries , Female , Infant , Infant, Newborn , Humans , Child, Preschool , Cohort Studies , Dental Caries/epidemiology , Australia , Diet , Sugars
3.
J Dent ; 134: 104559, 2023 07.
Article in English | MEDLINE | ID: mdl-37230240

ABSTRACT

OBJECTIVES: To investigate the association between trajectories of free sugars intake during the first five years of life and dental caries experience at five years. METHODS: Data from the SMILE population-based prospective birth cohort study, collected at one, two and five years old, were used. A 3-days dietary diary and food frequency questionnaire were used to estimate free sugars intake (FSI) in grams. The primary outcomes were dental caries prevalence and experience (dmfs). The Group-Based Trajectory Modelling method was used to characterize three FSI trajectories ('Low and increasing'; 'Moderate and increasing'; and 'High and increasing'), which were the main exposures. Multivariable regression models were generated to compute adjusted prevalence ratios (APR) and rate ratios (ARR) for the exposure, controlling for socioeconomic factors. RESULTS: The prevalence of caries was 23.3%, with a mean dmfs of 1.4, and a median of 3.0 among those who had caries. There were clear gradients of caries prevalence and experience by the FSI trajectories. The 'High and increasing' had an APR of 2.13 (95%CI 1.23-3.70) and ARR of 2.77 (95%CI 1.45-5.32) against the 'Low and increasing'. The 'Moderate and increasing' group had intermediate estimates. A quarter of the caries cases could have been prevented if the whole study sample had been in the 'Low and increasing' FSI trajectory. CONCLUSION: A sustained, high trajectory of FSI from a young age was positively associated with child dental caries. Measures to minimise consumption of free sugars must commence early in life. CLINICAL SIGNIFICANCE: The study has provided high level evidence to inform clinicians' decisions in promoting a healthy dietary pattern for young children.


Subject(s)
Dental Caries , Humans , Child, Preschool , Dental Caries/epidemiology , Cohort Studies , Prospective Studies , Dietary Sucrose/adverse effects , Prevalence
4.
BMC Public Health ; 22(1): 1203, 2022 06 16.
Article in English | MEDLINE | ID: mdl-35710413

ABSTRACT

BACKGROUND: In 2016, we conducted a systematic review to assess the feasibility of treatment monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in low and middle-income countries (LMICs), in line with the 90-90-90 treatment target. By 2020, global estimates suggest the 90-90-90 target, particularly the last 90, remains unattainable in many LMICs. This study aims to review the progress and identify needs for public health interventions to improve viral load monitoring and viral suppression for PLHIV in LMICs. METHODS: A literature search was conducted using an update of the initial search strategy developed for the 2016 review. Electronic databases (Medline and PubMed) were searched to identify relevant literature published in English between Dec 2015 and August 2021. The primary outcome was initial viral load (VL) monitoring (the proportion of PLHIV on ART and eligible for VL monitoring who received a VL test). Secondary outcomes included follow-up VL monitoring (the proportion of PLHIV who received a follow-up VL after an initial elevated VL test), confirmation of treatment failure (the proportion of PLHIV who had two consecutive elevated VL results) and switching treatment regimen rates (the proportion of PLHIV who switched treatment regimen after confirmation of treatment failure). RESULTS: The search strategy identified 1984 non-duplicate records, of which 34 studies were included in the review. Marked variations in initial VL monitoring coverage were reported across study settings/countries (range: 12-93% median: 74% IQR: 46-82%) and study populations (adults (range: 25-96%, median: 67% IQR: 50-84%), children, adolescents/young people (range: 2-94%, median: 72% IQR: 47-85%), and pregnant women (range: 32-82%, median: 57% IQR: 43-71%)). Community-based models reported higher VL monitoring (median: 85%, IQR: 82-88%) compared to decentralised care at primary health facility (median: 64%, IRQ: 48-82%). Suboptimal uptake of follow-up VL monitoring and low regimen switching rates were observed. CONCLUSIONS: Substantial gaps in VL coverage across study settings and study populations were evident, with limited data availability outside of sub-Saharan Africa. Further research is needed to fill the data gaps. Development and implementation of innovative, community-based interventions are required to improve VL monitoring and address the "failure cascade" in PLHIV on ART who fail to achieve viral suppression.


Subject(s)
Anti-HIV Agents , HIV Infections , Adolescent , Adult , Anti-HIV Agents/therapeutic use , Child , Female , HIV Infections/drug therapy , Humans , Pregnancy , Serologic Tests , Treatment Failure , Viral Load
5.
Eur J Ophthalmol ; 32(5): 2747-2751, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34761684

ABSTRACT

PURPOSE: To determine the incidence of ocular adverse effects (AEs) following brolucizumab injection for neovascular age-related macular degeneration at a tertiary academic institution. DESIGN: Retrospective, single center cohort study. PARTICIPANTS: All patients who received an intravitreal injection of brolucizumab 6 mg for neovascular age-related macular degeneration between October 7, 2019 and July 31, 2020. METHODS: Medical records of all patients who received brolucizumab 6 mg during the aforementioned time period were carefully reviewed and all ocular adverse effects after injection were charted. MAIN OUTCOME MEASURES: Incidence of post-injection ocular AEs, including intraocular inflammation (IOI), and time to development of AEs after injection. RESULTS: A total of 77 patients received brolucizumab 6 mg for a total of 115 administrations during the study period. There were 4 AEs (3.5%), including three cases of IOI (2.6%), one central retinal artery occlusion, and one retinal detachment. Two men and two women were affected. CONCLUSION: Ocular AEs, including those leading to severe vision loss, may develop after intravitreal brolucizumab 6 mg. A careful discussion of benefits and risks to brolucizumab should be conducted with all patients. PRECIS: In this first case series of ocular adverse effects after brolucizumab 6 mg injection at a single tertiary care center, the incidence of ocular adverse effects was 3.5%, including a 2.6% incidence of intraocular inflammation.


Subject(s)
Macular Degeneration , Uveitis , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized , Cohort Studies , Female , Humans , Inflammation , Intravitreal Injections , Macular Degeneration/drug therapy , Male , Retrospective Studies , Tertiary Care Centers , Uveitis/drug therapy , Visual Acuity
6.
JAMA Ophthalmol ; 139(8): 887-894, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34196692

ABSTRACT

IMPORTANCE: Big data studies may allow for the aggregation of patients with rare diseases such as uveitis to answer important clinical questions. Standardization of uveitis-related variables will be necessary, including the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes used to identify patients of interest. There are currently limited data on the uniformity of diagnosis mapping to ICD-10 codes for uveitis diagnoses among different health systems. OBJECTIVE: To assess the degree of uniformity in mapping of uveitis clinical concepts to ICD-10 codes across health care systems using the same electronic health record (EHR) system. DESIGN, SETTING, AND PARTICIPANTS: This multicenter survey study was conducted between September 14 and October 9, 2020, at 5 academic health care systems that use the Epic EHR. Researchers from the University of Washington, Harvard University, Stanford University, Yale University, and the University of California, San Francisco queried 54 uveitis-related diagnostic terms and recorded the associated ICD-10 codes. MAIN OUTCOMES AND MEASURES: The degree of uniformity for uveitis clinical concepts and associated ICD-10 codes. RESULTS: Fifty-four uveitis-related diagnostic terms were queried within the Epic EHR at 5 different health care systems. There was perfect agreement among all 5 centers for 52 of the 54 diagnostic terms. Two diagnostic terms had differences in ICD-10 coding: juvenile idiopathic arthritis associated chronic uveitis and intermediate uveitis. Intermediate uveitis was associated with codes H20.1x (ICD-10 description: chronic iridocyclitis) or H20.9 (ICD-10 description: unspecified iridocyclitis) in 3 centers while being associated with code H30.2x (ICD-10 description: posterior cyclitis) at the 2 remaining centers. The discrepancies appear to be related to a recent update in diagnostic mapping in the Epic EHR. CONCLUSIONS AND RELEVANCE: This study suggests that ICD-10 code mapping to uveitis diagnostic terminology appears to be highly uniform at different centers with the Epic EHR. However, temporal changes in diagnosis mapping to ICD-10 codes and a lack of 1-to-1 mapping of diagnosis to ICD-10 code add additional sources of complexity to the interpretation of big data studies in uveitis.


Subject(s)
Iridocyclitis , Uveitis, Intermediate , Uveitis , Delivery of Health Care , Electronic Health Records , Humans , International Classification of Diseases , Uveitis/diagnosis , Uveitis/epidemiology
7.
Int J STD AIDS ; 32(10): 911-918, 2021 09.
Article in English | MEDLINE | ID: mdl-33861666

ABSTRACT

Although Vietnam has promoted the utilisation of highly active antiretroviral therapy (HAART) towards HIV elimination targets, adherence to treatment has remained under-investigated. We aimed to describe high-risk behaviours and clinical characteristics by adherence status and to identify the factors associated with non-adherence. We included 426 people living with HIV (PLWH) currently or previously involved in HAART. Most participants were men (75.4%), young (33.6 years), with low income and low education levels. Non-adherent PLWH (11.5%) were more likely to have a larger number of sex partners (p-value = 0.053), sex without condom use (p-value = 0.007) and not receive result at hospital or voluntary test centre (p-value = 0.001). Multiple logistic regression analysis showed that demographic (education levels), sexual risk behaviours (multiple sex partners and sex without using condom) and clinical characteristics (time and facility at first time received HIV-positive result) were associated with HAART non-adherence. There are differences in associated factors between women (education levels and place of HIV testing) and men (multiple sex partners). Gender-specific programs, changing risky behaviours and reducing harms among PLWH may benefit adherence. We highlight the need to improve the quantity and quality of HIV/AIDS services in Vietnam, especially in pre- and post-test counselling, to achieve better HAART adherence, working towards ending AIDS in 2030.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections , Cross-Sectional Studies , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Risk-Taking , Vietnam/epidemiology
8.
AIDS ; 35(8): 1253-1262, 2021 07 01.
Article in English | MEDLINE | ID: mdl-33730746

ABSTRACT

OBJECTIVES: To estimate trends in and projections of annual HIV testing and condom use at last higher-risk sex and to calculate the probability of reaching key United Nations Programme on AIDS (UNAIDS)'s target. DESIGN: We included 114 nationally-representative datasets in 38 African countries from Demographic and Health Surveys and Multiple Indicator Cluster Surveys with 1 456 224 sexually active adults age 15-49 from 2003 to 2018. METHODS: We applied Bayesian mixed effect models to estimate the coverage of annual HIV testing and condom use at last higher-risk sex for every country and year to 2030 and the probability of reaching UNAIDS testing and condom use targets of 95% coverage by 2030. RESULTS: Seven countries saw downward trends in annual HIV testing and four saw decreases in condom use at higher-risk sex, whereas most countries have upward trends in both indicators. The highest coverage of testing in 2030 is predicted in Swaziland with 92.6% (95% credible interval: 74.5-98.1%), Uganda with 90.5% (72.2-97.2%), and Lesotho with 90.5% (69.4%-97.6%). Meanwhile, Swaziland, Lesotho, and Namibia will have the highest proportion of condom use in 2030 at 85.0% (57.8-96.1%), 75.6% (42.3-93.6%), and 75.5% (42.4-93.2%). The probabilities of reaching targets were very low for both HIV testing (0-28.5%) and condom use (0-12.1%). CONCLUSIONS: We observed limited progress on annual HIV testing and condom use at last higher-risk sex in Africa and little prospect of reaching global targets for HIV/AIDS elimination. Although some funding agencies are considering withdrawal from supporting Africa, more attention to funding and expanding testing and treatment is needed in this region.


Subject(s)
Condoms , HIV Infections , Adolescent , Adult , Bayes Theorem , Eswatini , HIV Infections/diagnosis , HIV Infections/prevention & control , HIV Testing , Humans , Lesotho , Middle Aged , Namibia , Uganda , Young Adult
10.
J Neuroophthalmol ; 41(2): 217-223, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-32235230

ABSTRACT

BACKGROUND: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. METHODS: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. RESULTS: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. CONCLUSIONS: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.


Subject(s)
Gonadal Steroid Hormones/adverse effects , Intracranial Hypertension/chemically induced , Intracranial Pressure/drug effects , Sex Reassignment Procedures/methods , Transgender Persons , Adult , Female , Humans , Intracranial Hypertension/physiopathology , Male , Retrospective Studies , Young Adult
12.
Am J Ophthalmol Case Rep ; 19: 100825, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32715157

ABSTRACT

PURPOSE: To report a case of bilateral pan-uveitis resembling fungal and viral endophthalmitis in a patient who was ultimately diagnosed with sarcoidosis. OBSERVATION: A 64-year-old female presented with a four-day history of painless vision loss in the right eye. She presented with multiple concurrent systemic complaints, including a history of oral and genital sores, patches of hypopigmented skin on her forearms, and occasional shortness of breath. Upon further examination, she was noted to have bilateral pan-uveitis, which was more severe in the right than left eye. Posterior pole examination of the right eye revealed dense vitritis with multiple large whitish round balls that seemed suggestive of fungal or viral endophthalmitis. Initial therapies included intravitreal (IVT) foscarnet and intravenous (IV) acyclovir, followed by IV amphotericin B and oral voriconazole, which did not improve ocular signs and symptoms. Further evaluations ruled out infectious etiologies and lymphoma. Chest computerized tomography (CT) scan revealed findings suggestive of sarcoidosis, which was confirmed with lung biopsy. Anti-viral and -fungal treatments were discontinued, and the patient was started on IV methylprednisolone followed by oral prednisone and mycophenolate mofetil. Ocular symptoms improved, and the patient remained stable after treatment. CONCLUSION AND IMPORTANCE: The index report illustrates a case of ocular sarcoidosis that imitated the presentation of infectious endophthalmitis. Though ocular sarcoidosis is known to masquerade as a range of disorders and constitutes part of the differential diagnosis for infectious endophthalmitis, sarcoidosis has not been reported in recent literature to imitate the presentation of fungal endophthalmitis. The index case suggests that ocular sarcoidosis should be considered in the differential diagnoses of fungal endophthalmitis.

13.
PLoS One ; 15(5): e0232353, 2020.
Article in English | MEDLINE | ID: mdl-32369500

ABSTRACT

IMPORTANCE: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness with several intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents available for its management such as aflibercept, bevacizumab, and ranibizumab. However, direct comparisons between these three agents among the same patient population are limited. OBJECTIVE: To assess the rate and growth of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in eyes with nAMD treated with aflibercept, bevacizumab, and/or ranibizumab. METHOD: Retrospective cohort study of patients with treatment-naïve neovascular AMD seen at an academic hospital between October 2006 and February 2019. Study eyes were treated with intravitreal injections of aflibercept, bevacizumab, and/or ranibizumab and followed for two years. MAIN OUTCOMES AND MEASURES: cRORA prevalence, location, size, and growth rate. Eyes were imaged with Cirrus spectral domain optical coherence tomography (SD-OCT). Presence and size of cRORA were calculated using the FDA-approved Advanced RPE Analysis software. Linear regression models were used to correlate cRORA progression with baseline demographic and ocular characteristics, anti-VEGF drug, and number of injections. Unpaired t-tests, ANOVA, and linear regression models were computed with SAS 9.4. RESULTS: 197 eyes from 158 patients (mean age 78.9, 62.9% women) received an average of 13 anti-VEGF injections over 24 months. 22% developed new cRORA. Mean cRORA area increased from 1.71 mm2 to 2.93 mm2. At 24 months, eyes with 11+ injections had significantly less cRORA area (11+ injections, 4.02 mm2; ≤ 10 injections, 2.46 mm2; p = 0.01) and growth rate (11+ injections, 0.41 mm2/year; ≤ 10 injections, 1.05 mm2/year; p = 0.02). Choice of anti-VEGF drug yielded no significant difference in cRORA progression. CONCLUSIONS AND RELEVANCE: Treating nAMD with aflibercept, bevacizumab or ranibizumab demonstrated comparable cRORA development at 24 months. Number of injections inversely correlated with cRORA area and growth. These results warrant further investigation in the pathophysiology of cRORA in anti-VEGF treated eyes.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Retinal Degeneration/drug therapy , Retinal Degeneration/pathology , Retinal Pigment Epithelium/drug effects , Retinal Pigment Epithelium/pathology , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Aged, 80 and over , Atrophy , Bevacizumab/therapeutic use , Female , Follow-Up Studies , Humans , Image Interpretation, Computer-Assisted , Intravitreal Injections , Male , Ranibizumab/therapeutic use , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Retinal Degeneration/diagnostic imaging , Retinal Pigment Epithelium/diagnostic imaging , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome
14.
Chembiochem ; 21(17): 2487-2494, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32255248

ABSTRACT

Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group and either a thyminyl or methylthyminyl group have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1-(S,Rp ), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1-(S,Rp ), which only differs from the lead compound in being substituted on two cyclopentadienyl rings rather than one, was over 20 times less cytotoxic. On the other hand, methylated derivatives of 1-(S,Rp ) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1-(S,Rp ) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity.


Subject(s)
Antineoplastic Agents/pharmacology , Bone Neoplasms/drug therapy , Ferrous Compounds/pharmacology , Metallocenes/pharmacology , Nucleosides/pharmacology , Organometallic Compounds/pharmacology , Osteosarcoma/drug therapy , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Bone Neoplasms/pathology , Cell Proliferation/drug effects , Cell Survival/drug effects , Crystallography, X-Ray , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Ferrous Compounds/chemistry , Humans , Metallocenes/chemistry , Methylation , Models, Molecular , Molecular Structure , Nucleosides/chemistry , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Osteosarcoma/pathology , Structure-Activity Relationship , Tumor Cells, Cultured
15.
Dalton Trans ; 49(4): 1181-1190, 2020 Jan 28.
Article in English | MEDLINE | ID: mdl-31897458

ABSTRACT

A new chiral organometallic nucleoside analogue containing ruthenocene is reported, in which alkylthymine and alkylhydroxyl groups are attached in adjacent positions on one cyclopentadienyl ring. The synthetic procedures for this metallocene derivative and two control compounds are described, along with their characterisation by cyclic voltammetry and X-ray crystallography. Their biological activities in a human pancreatic cancer cell line (MIA-Pa-Ca-2) were significantly lower than those of three previously reported analogous ferrocene compounds, indicating that the choice of metallocene metal atom (Fe or Ru) plays a pivotal role in determining the anticancer properties of these nucleoside analogues, which in turn suggests a different mode of action from that of a conventional nucleoside analogue.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Metallocenes/chemistry , Metallocenes/pharmacology , Nucleosides/chemistry , Cell Line, Tumor , Electrochemistry , Humans , Inhibitory Concentration 50 , Models, Molecular , Molecular Conformation
17.
Glob Heart ; 14(2): 143-147, 2019 06.
Article in English | MEDLINE | ID: mdl-31324368

ABSTRACT

BACKGROUND: Stakeholder engagement is crucial for conducting high-quality implementation research as well as for the incorporation and adoption of health interventions and policies in the community. OBJECTIVES: This study sought to build a mutually rewarding collaboration between stakeholders in Vietnam and investigators in the United States. METHODS: A collaboration was established between investigators from several institutions in Vietnam and the University of Massachusetts Medical School that was built on mutual trust, cross-cultural learning, and shared experiences. This collaborative arrangement has led to sustainable stakeholder engagement in Vietnam. We formed a multidisciplinary transnational research team and maintained regular contact both online and in person. We also conducted a needs assessment study, in which several focus group discussions and in-depth interviews of stakeholders in Vietnam were carried out. RESULTS: The formal collaboration between investigators in Vietnam and the University of Massachusetts Medical School began in 2011 and has strengthened over time. The U.S. team provided expertise in study and intervention design, data collection and analysis, and trial implementation, whereas the team in Vietnam brought a deep understanding of local health care delivery systems and expertise in the delivery of health care interventions at the grassroots level. Our initial partnership has now grown to include committed individuals at the government, academic, and community levels including the Vietnam Ministry of Health, key governmental and nongovernmental research institutions and agencies, medical and public health universities, and communities in rural settings. The needs assessment study found that there are important gaps in the delivery of hypertension management practices in many rural communities in Vietnam and that stakeholders are fully engaged in our ongoing, community-based, hypertension-control project. CONCLUSIONS: Multiple layers of stakeholders and communities in Vietnam are fully engaged with, and have contributed significantly to, our ongoing hypertension control research project in Northern Vietnam.


Subject(s)
Noncommunicable Diseases/prevention & control , Rural Population , Stakeholder Participation , Translational Research, Biomedical/methods , Data Collection , Developing Countries , Humans , Income , Noncommunicable Diseases/epidemiology , Prevalence , Vietnam/epidemiology
18.
Int J Gynaecol Obstet ; 144(1): 21-26, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30353543

ABSTRACT

OBJECTIVES: To determine the relationship between maternal serum uric acid levels and fetal/neonatal complications in women with pre-eclampsia/eclampsia, and to establish a predictive threshold value. METHODS: A diagnostic test and historical cohort study conducted by prospective cross-sectional data collection on pregnant women with pre-eclampsia/eclampsia at Hue University Hospital, Vietnam, between March 2015 and July 2017. Pre-eclampsia was diagnosed based on ACOG criteria. Serum uric acid levels were measured by enzymatic colorimetric testing using a Cobas c 501 analyzer (Roche Diagnostics, Mannheim, Germany). Fetal complications included intrauterine growth restriction, preterm delivery, fetal death, and neonatal death. RESULTS: There were 205 women enrolled. Serum uric acid at a cutoff of 393 µmol/L is a good predictor of fetal/neonatal complications (AUC 0.752), with 64.4% sensitivity and 79.5% specificity. High uric acid level (≥393 µmol/L) resulted in increased risk of preterm birth (OR 6.367, 95% CI 3.009-13.084), low Apgar scores (OR 5.514, 95% CI 1.877-16.198), intrauterine growth restriction (OR 7.188, 95% CI 3.592-14.382), and neonatal death (OR 7.818, 95% CI 1.614-37.867). There was no relationship between uric acid level and fetal death (OR 1.803, 95% CI 0.355-9.168). CONCLUSIONS: Maternal serum uric acid concentration is a good predictor of fetal/neonatal outcomes in women with pre-eclampsia/eclampsia.


Subject(s)
Eclampsia/blood , Fetal Growth Retardation/blood , Pre-Eclampsia/blood , Premature Birth/blood , Uric Acid/blood , Adult , Apgar Score , Cross-Sectional Studies , Female , Fetal Growth Retardation/etiology , Humans , Infant, Newborn , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , Premature Birth/etiology , Prospective Studies , Severity of Illness Index , Vietnam
19.
Biomed Res Int ; 2018: 2370284, 2018.
Article in English | MEDLINE | ID: mdl-30596085

ABSTRACT

The proportion of elderly people in big cities of developing countries, including Vietnam, is rapidly increasing during the age of rampant urbanization. This is being followed by a sustained rise of illnesses, especially mental health issues. The objective of this study was to analyze the association between depression and the factors associated with depression among the elderly. In a cross-sectional study, 299 elderly living in Hanoi, Vietnam, were approached for data collection. Self-reported depression among the elderly was 66.9% (32.8% mild, 30.4% moderate, and 3.7% severe cases). In multivariate analysis, there were significant associations between age, number of physical activities, number of medicine intake, and 3 domains of quality of life (physical health, psychological health, and environmental health) and depression. Age and the number of medicine intake are positively correlated with depression, accounting for 57.94% and 58.93%, respectively. On the contrary, the number of physical activities and the 3 domains of quality life mentioned above are negatively correlated with depression. In the urban setting of a developing country like Vietnam, the elderly have experienced common depression. Recognizing depression among the elderly-which is individual and social-helps us design public health programs. Screening for early depression, joining social programming, and participating in physical activities may improve the mental life of the elderly.


Subject(s)
Activities of Daily Living/psychology , Depression/psychology , Depressive Disorder/psychology , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Mental Health , Middle Aged , Quality of Life/psychology , Urban Population , Vietnam
20.
Surv Ophthalmol ; 63(4): 589-594, 2018.
Article in English | MEDLINE | ID: mdl-28986312

ABSTRACT

Over a 2-year period, swellings of all 4 eyelid margins developed in a 32-year-old woman and was accompanied by complete loss of eyelashes. An inflammatory dermatologic condition was considered the most likely cause. A full-thickness right lower eyelid biopsy revealed a multinodular lymphoid tumor at the eyelid margin which immunophenotypically and genetically was diagnosed as an extranodal marginal zone lymphoma. The mode of presentation of the disease was considered to be most unusual, as was its B cell lineage, since the majority of primary cutaneous lymphomas are of T-cell origin. Systemic workup demonstrated bilateral involvement of the external auditory canals.


Subject(s)
Eyelashes/pathology , Eyelid Neoplasms/complications , Hair Diseases/etiology , Lymphoma, B-Cell, Marginal Zone/complications , Adult , Female , Humans
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