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1.
EMBO J ; 43(4): 568-594, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38263333

RESUMO

Comprehensive analysis of cellular dynamics during the process of morphogenesis is fundamental to understanding the principles of animal development. Despite recent advancements in light microscopy, how successive cell shape changes lead to complex three-dimensional tissue morphogenesis is still largely unresolved. Using in vivo live imaging of Drosophila wing development, we have studied unique cellular structures comprising a microtubule-based membrane protrusion network. This network, which we name here the Interplanar Amida Network (IPAN), links the two wing epithelium leaflets. Initially, the IPAN sustains cell-cell contacts between the two layers of the wing epithelium through basal protrusions. Subsequent disassembly of the IPAN involves loss of these contacts, with concomitant degeneration of aligned microtubules. These processes are both autonomously and non-autonomously required for mitosis, leading to coordinated tissue proliferation between two wing epithelia. Our findings further reveal that a microtubule organization switch from non-centrosomal to centrosomal microtubule-organizing centers (MTOCs) at the G2/M transition leads to disassembly of non-centrosomal microtubule-derived IPAN protrusions. These findings exemplify how cell shape change-mediated loss of inter-tissue contacts results in 3D tissue morphogenesis.


Assuntos
Drosophila , Microtúbulos , Animais , Microtúbulos/metabolismo , Epitélio/metabolismo , Centro Organizador dos Microtúbulos/metabolismo , Morfogênese
2.
Nature ; 601(7893): 452-459, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34912117

RESUMO

Structure-based virtual ligand screening is emerging as a key paradigm for early drug discovery owing to the availability of high-resolution target structures1-4 and ultra-large libraries of virtual compounds5,6. However, to keep pace with the rapid growth of virtual libraries, such as readily available for synthesis (REAL) combinatorial libraries7, new approaches to compound screening are needed8,9. Here we introduce a modular synthon-based approach-V-SYNTHES-to perform hierarchical structure-based screening of a REAL Space library of more than 11 billion compounds. V-SYNTHES first identifies the best scaffold-synthon combinations as seeds suitable for further growth, and then iteratively elaborates these seeds to select complete molecules with the best docking scores. This hierarchical combinatorial approach enables the rapid detection of the best-scoring compounds in the gigascale chemical space while performing docking of only a small fraction (<0.1%) of the library compounds. Chemical synthesis and experimental testing of novel cannabinoid antagonists predicted by V-SYNTHES demonstrated a 33% hit rate, including 14 submicromolar ligands, substantially improving over a standard virtual screening of the Enamine REAL diversity subset, which required approximately 100 times more computational resources. Synthesis of selected analogues of the best hits further improved potencies and affinities (best inhibitory constant (Ki) = 0.9 nM) and CB2/CB1 selectivity (50-200-fold). V-SYNTHES was also tested on a kinase target, ROCK1, further supporting its use for lead discovery. The approach is easily scalable for the rapid growth of combinatorial libraries and potentially adaptable to any docking algorithm.


Assuntos
Algoritmos , Técnicas de Química Combinatória , Descoberta de Drogas , Bibliotecas Digitais , Ligantes , Simulação de Acoplamento Molecular , Quinases Associadas a rho
3.
Plant Cell ; 34(1): 455-476, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34718767

RESUMO

Stomatal pores and the leaf cuticle regulate evaporation from the plant body and balance the tradeoff between photosynthesis and water loss. MYB16, encoding a transcription factor involved in cutin biosynthesis, is expressed in stomatal lineage ground cells, suggesting a link between cutin biosynthesis and stomatal development. Here, we show that the downregulation of MYB16 in meristemoids is directly mediated by the stomatal master transcription factor SPEECHLESS (SPCH) in Arabidopsis thaliana. The suppression of MYB16 before an asymmetric division is crucial for stomatal patterning, as its overexpression or ectopic expression in meristemoids increased stomatal density and resulted in the formation of stomatal clusters, as well as affecting the outer cell wall structure. Expressing a cutinase gene in plants ectopically expressing MYB16 reduced stomatal clustering, suggesting that cutin affects stomatal signaling or the polarity setup in asymmetrically dividing cells. The clustered stomatal phenotype was rescued by overexpressing EPIDERMAL PATTERNING FACTOR2, suggesting that stomatal signaling was still functional in these plants. Growing seedlings ectopically expressing MYB16 on high-percentage agar plates to modulate tensile strength rescued the polarity and stomatal cluster defects of these seedlings. Therefore, the inhibition of MYB16 expression by SPCH in the early stomatal lineage is required to correctly place the polarity protein needed for stomatal patterning during leaf morphogenesis.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Divisão Celular Assimétrica/genética , Polaridade Celular/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Estômatos de Plantas/fisiologia , Fatores de Transcrição/genética , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo
4.
Dev Biol ; 481: 43-51, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555363

RESUMO

Developmental patterning is thought to be regulated by conserved signalling pathways. Initial patterns are often broad before refining to only those cells that commit to a particular fate. However, the mechanisms by which pattern refinement takes place remain to be addressed. Using the posterior crossvein (PCV) of the Drosophila pupal wing as a model, into which bone morphogenetic protein (BMP) ligand is extracellularly transported to instruct vein patterning, we investigate how pattern refinement is regulated. We found that BMP signalling induces apical enrichment of Myosin II in developing crossvein cells to regulate apical constriction. Live imaging of cellular behaviour indicates that changes in cell shape are dynamic and transient, only being maintained in those cells that retain vein fate competence after refinement. Disrupting cell shape changes throughout the PCV inhibits pattern refinement. In contrast, disrupting cell shape in only a subset of vein cells can result in a loss of BMP signalling. We propose that mechano-chemical feedback leads to competition for the developmental signal which plays a critical role in pattern refinement.


Assuntos
Padronização Corporal , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Transdução de Sinais , Animais , Proteínas Morfogenéticas Ósseas/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Pupa , Asas de Animais
5.
Dev Dyn ; 251(1): 198-212, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34241935

RESUMO

Bone morphogenetic proteins (BMPs), members of the transforming growth factor-ß (TGF-ß) family, have been shown to contribute to embryogenesis and organogenesis during animal development. Relevant studies provide support for the following concepts: (a) BMP signals are evolutionarily highly conserved as a genetic toolkit; (b) spatiotemporal distributions of BMP signals are precisely controlled at the post-translational level; and (c) the BMP signaling network has been co-opted to adapt to diversified animal development. These concepts originated from the historical findings of the Spemann-Mangold organizer and the subsequent studies about how this organizer functions at the molecular level. In this Commentary, we focus on two topics. First, we review how the BMP morphogen gradient is formed to sustain larval wing imaginal disc and early embryo growth and patterning in Drosophila. Second, we discuss how BMP signal is tightly controlled in a context-dependent manner, and how the signal and tissue dynamics are coupled to facilitate complex tissue structure formation. Finally, we argue how these concepts might be developed in the future for further understanding the significance of BMP signaling in animal development.


Assuntos
Proteínas de Drosophila , Regulação da Expressão Gênica no Desenvolvimento , Animais , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Drosophila/genética , Proteínas de Drosophila/genética , Ligantes , Asas de Animais/metabolismo
6.
Dev Biol ; 476: 240-248, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33864778

RESUMO

Female fertility in mammals requires iterative remodeling of the entire adult female reproductive tract across the menstrual/estrous cycle. However, while transcriptome dynamics across the estrous cycle have been reported in human and bovine models, no global analysis of gene expression across the estrous cycle has yet been reported for the mouse. Here, we examined the cellular composition and global transcriptional dynamics of the mouse oviduct along the anteroposterior axis and across the estrous cycle. We observed robust patterns of differential gene expression along the anteroposterior axis, but we found surprisingly few changes in gene expression across the estrous cycle. Notable gene expression differences along the anteroposterior axis included a surprising enrichment for genes related to embryonic development, such as Hox and Wnt genes. The relatively stable transcriptional dynamics across the estrous cycle differ markedly from other mammals, leading us to speculate that this is an evolutionarily derived state that may reflect the extremely rapid five-day mouse estrous cycle. This dataset fills a critical gap by providing an important genomic resource for a highly tractable genetic model of mammalian female reproduction.


Assuntos
Fertilidade/genética , Oviductos/metabolismo , Transcriptoma/genética , Animais , Desenvolvimento Embrionário/genética , Ciclo Estral/genética , Feminino , Fertilidade/fisiologia , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Camundongos , Oviductos/fisiologia , Gravidez
7.
Biochem Biophys Res Commun ; 591: 31-36, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34995983

RESUMO

2-Arachidonoylglycerol (2-AG) is the most potent and abundant endocannabinoid that acts as a full agonist at the cannabinoid 1 (CB1) and 2 (CB2) receptors. It serves as a substrate for several serine hydrolases, including monoacylglycerol lipase (MGL), α/ß hydrolase domain 6 (ABHD6) and fatty acid amide hydrolase (FAAH). However, 2-AG's rapid conversion to 1-AG (the S stereoisomer) and 3-AG (the R stereoisomer) complicates in vivo signaling. Here, we present the interaction profiles of 2-AG and its isomerization products, 1- and 3-AG, with the endocannabinoid MGL, ABHD6 and FAAH enzymes as well as the CB1 receptor. The 1- and 3-AG enantiomers are less prone to isomerization, and their affinities to endocannabinoid enzymes and potencies at CB1 receptor are quite different compared to 2-AG. Although MGL is the principal hydrolytic enzyme of 2-AG, 3-AG (the R isomer) appears to be the best substrate for hMGL. Contrarily, 1-AG (the S isomer) demonstrates the worst substrate profile, indicating that the stereochemistry of 1(3)-monoacylglycerols is very important for MGL enzyme. On the other hand, both 1- and 3-AG (the sn1 monoacylglycerols) are efficiently hydrolyzed by hABHD6 without preference, while 2-AG (the sn2 monoacylglycerol) has the lowest rate of hydrolysis. FAAH, the principal hydrolytic enzyme for arachidonoylethanolamide (anandamide, AEA), catalyzes the hydrolysis of all three isomers with similar efficiencies. In a functional cAMP assay at CB1 receptor, all three isomers behaved as agonists, with 2-AG being the most potent, followed by 3-AG then 1-AG. The presented data provides stereochemical insights to design chemically stable AG analogs with preferential stability against enzymes of interest.


Assuntos
Ácidos Araquidônicos/metabolismo , Endocanabinoides/metabolismo , Glicerídeos/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Amidoidrolases/metabolismo , Ácidos Araquidônicos/química , Soluções Tampão , Cromatografia Líquida de Alta Pressão , AMP Cíclico/metabolismo , Endocanabinoides/química , Glicerídeos/química , Células HEK293 , Humanos , Hidrólise , Isomerismo , Cinética , Ligantes , Monoacilglicerol Lipases/metabolismo , Especificidade por Substrato
8.
J Clin Pharm Ther ; 47(12): 2014-2019, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35848069

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Allopurinol, the first-line medication for hyperuricemia is well-known for its association with severe cutaneous adverse reactions, especially Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the current study, we analysed the Vietnamese spontaneous reporting database to identify signals and preventability of allopurinol-induced SJS/TEN in Vietnam from 2010 to 2019. METHODS: Signal generation was assessed using the case/non-case method. Reporting odds ratios (RORs) and 95% confidence intervals (95% CI) were calculated. RESULTS: Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830-6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508-16.710). The preventability assessment showed that no allopurinol-induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy. WHAT IS NEW AND CONCLUSION: The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 and annually increased until 2019. Our first report specifically focusing on the ADR preventability of allopurinol showed that correction of medical errors relating to prescription could prevent more than 60% of SJS/TEN cases in Vietnamese allopurinol users. This is a feasible and practical solution, provided that there would be a systematic change in both healthcare systems and public awareness.


Assuntos
Hiperuricemia , Síndrome de Stevens-Johnson , Humanos , Alopurinol/efeitos adversos , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/prevenção & controle , Farmacovigilância , Vietnã , Hiperuricemia/tratamento farmacológico
9.
Bioorg Med Chem Lett ; 38: 127882, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33636308

RESUMO

As a continuation of earlier work on classical cannabinoids bearing bulky side chains we report here the design, synthesis, and biological evaluation of 3'-functionalized oxa-adamantyl cannabinoids as a novel class of cannabinergic ligands. Key synthetic steps involve nucleophilic addition/transannular cyclization of aryllithium to epoxyketone in the presence of cerium chloride and stereoselective construction of the tricyclic cannabinoid nucleus. The synthesis of the oxa-adamantyl cannabinoids is convenient, and amenable to scale up allowing the preparation of these analogs in sufficient quantities for detailed in vitro evaluation. The novel oxa-adamantyl cannabinoids reported here were found to be high affinity ligands for the CB1 and CB2 cannabinoid receptors. In the cyclase assay these compounds were found to behave as potent and efficacious CB1 receptor agonists. Isothiocyanate analog AM10504 is capable of irreversibly labeling both the CB1 and CB2 receptors.


Assuntos
Canabinoides/farmacologia , Receptor CB1 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/agonistas , Canabinoides/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
10.
Dev Dyn ; 249(7): 898-905, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32133718

RESUMO

BACKGROUND: In mammals, multiciliated cells (MCCs) line the lumen of the trachea, oviduct, and brain ventricles, where they drive fluid flow across the epithelium. Each MCC population experiences vastly different local environments that may dictate differences in their lifetime and turnover rates. However, with the exception of MCCs in the trachea, the turnover rates of these multiciliated epithelial populations at extended time scales are not well described. RESULTS: Here, using genetic lineage-labeling techniques we provide a direct comparison of turnover rates of MCCs in these three different tissues. CONCLUSION: We find that oviduct turnover is similar to that in the airway (~6 months), while multiciliated ependymal cells turnover more slowly.


Assuntos
Encéfalo/crescimento & desenvolvimento , Cílios/metabolismo , Oviductos/crescimento & desenvolvimento , Traqueia/crescimento & desenvolvimento , Alelos , Animais , Diferenciação Celular/genética , Células Epiteliais , Epitélio , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Fluorescência Verde/metabolismo , Homeostase , Camundongos , Transdução de Sinais
11.
Platelets ; 31(4): 505-512, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31366263

RESUMO

Thalassemia patients are susceptible to both iron overload and thromboembolism. Deferiprone is an iron chelator that shows an antiplatelet activity and thus may alleviate platelet hyperactivation in thalassemia. Therefore, this study aimed to characterize the inhibitory effects and mechanisms of deferiprone on normal human platelets. The results illustrated that deferiprone inhibited platelet aggregation at the iron chelating concentrations (0.08-0.25 mmol/l). Deferiprone inhibited human platelet aggregation stimulated by arachidonic acid and ADP more potently than epinephrine and collagen, with the IC50 of 0.24 mmol/l and 0.25 mmol/l vs. 3.36 mmol/l and 3.73 mmol/l, respectively. Interestingly, deferiprone significantly inhibited COX-1 activity, with the IC50 of 0.33 mmol/l, and slightly increased cAMP level at the high concentration of 4 mmol/l. Moreover, the results from molecular docking showed that deferiprone interacted closely with key residues in the peroxidase active site of COX-1. These results suggested that deferiprone possessed antiplatelet activity mainly through the inhibition of COX-1 activity.


Assuntos
Plaquetas/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Deferiprona/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Adolescente , Ácido Araquidônico/farmacologia , Plaquetas/enzimologia , Plaquetas/metabolismo , AMP Cíclico/metabolismo , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/genética , Deferiprona/química , Humanos , Concentração Inibidora 50 , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Adulto Jovem
12.
J Clin Pharm Ther ; 45(1): 122-127, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31486525

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Under-reporting is a major drawback of a voluntary adverse drug reaction reporting system in pharmacovigilance. However, little is known about facilitators and barriers to ADR reporting by healthcare professionals (HCPs) in developing countries. To investigate factors associated with adverse drug reaction (ADR) reporting among HCPs in Vietnam. METHODS: A cross-sectional survey of 2091 HCPs was conducted in 2015 at 10 hospitals throughout Vietnam. The binary outcome was ever reporting ADRs. Healthcare professionals knowledge, attitude and practice about ADR reporting were measured. Multiple logistic regression analyses examined factors significantly associated with ever ADR reporting. RESULTS: Overall, 29.3%, 2.2% and 68.4% of the sample were doctors, pharmacists and nurses, respectively. More than half (59.3%) had ever reported any ADR. Facilitators for ADR reporting were educational training (OR = 1.77, 95%CI = 1.42-2.22) and having better knowledge, such as awareness of ADR reporting regulation (OR = 1.63, 95%CI = 1.19-2.21), of reporting time (OR = 1.76, 95%CI = 1.35-2.29) and of necessary information in reporting form (OR = 1.94, 95%CI = 1.53-2.45).Conversely, barriers to non-reporting were unknown of reporting procedure (OR = 0.27, 95%CI = 0.22-0.35), unavailability of reporting form (OR = 0.54, 95%CI = 0.42-0.68) and lack of time (OR = 0.59, 95%CI = 0.46-0.74). WHAT IS NEW AND CONCLUSION: Given the low ADR reporting rate among HCPs, educational interventions to improve their knowledge and attitude should be prioritized in Vietnam. Additional interventions addressing obstacles (i.e. availability and complexity of reporting form, lack of time) should be considered to improve both the quantity and quality of ADR reporting.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Pessoal de Saúde/estatística & dados numéricos , Farmacovigilância , Adulto , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Inquéritos e Questionários , Vietnã
13.
Surg Innov ; 26(5): 560-572, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31130082

RESUMO

Purpose. To investigate the knowledge, attitude, and practice of surgeons toward introducing novel surgical techniques in Egypt, Palestine, and Vietnam. Summary Background Data. Despite the recent advances in modern surgical care and its role in advancing the quality and the length of lives, surgery in the developing world has stagnated or even regressed. Methods. A survey was undertaken among the surgeons in 9 hospitals belonging to the 3 countries. Questions were categorized into knowledge, attitude, and practice questions. Meta-analyses were performed to estimate the event rate and compare between knowledge and practice, senior and junior surgeons. Results. A total of 244 responses, with a response rate of 79.7%, were included in the analysis. Regarding knowledge and attitude, the results were satisfactory except that only 55.8% of surgeons appraised their level of education and 43.3% wanted to earn money from the novel procedure. There was a significant difference between knowledge and practice regarding getting informed consent from the patients (P = .024), discussing the novelty of the procedure (P < .001), discussing the alternative procedures (P < .001), discussing the surgeons' experience and level of skills (P < .001), discussing the risk of the new procedure (P < .001), and monitoring the outcomes after the new procedure (P < .001). Conclusions. Most surgeons have sufficient knowledge and are motivated regarding adopting novel surgical techniques in order to provide the best care for the patients. However, there was a gap between knowledge and practice. Training programs and evidence-based guidelines regarding the introduction of novel surgical techniques are needed to overcome these challenges.


Assuntos
Difusão de Inovações , Conhecimentos, Atitudes e Prática em Saúde , Cirurgiões/psicologia , Procedimentos Cirúrgicos Operatórios/tendências , Adulto , Estudos Transversais , Egito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oriente Médio , Inquéritos e Questionários , Vietnã
14.
J Public Health Manag Pract ; 24 Suppl 2: S67-S73, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29369259

RESUMO

CONTEXT: Alcohol contributes to severe social and health problems and is a major risk factor for noncommunicable diseases in Vietnam. Over the years, there has been an increase in consumption per capita as well as a rapid expansion of commercially prepared alcohol. OBJECTIVE: To describe the prevalence of alcohol consumption and binge drinking in a random sample of people 15 years of age and older living in Chi Linh who were also a part of the Chi Linh Health and Demographic Surveillance System (CHILILAB HDSS) and to determine the association between alcohol use and sociodemographic characteristics. DESIGN: Data on alcohol consumption of 5438 people 15 years of age and older were extracted from the CHILILAB HDSS information collected in 2016. Descriptive statistics and multiple logistic regression were utilized to assess the association between current drinkers and binge drinkers with socioeconomic groups. RESULTS: The overall prevalence of alcohol use 1 month prior to interview was 41.1%, which is composed of 75.1% males and 17.3% females. Among the 41% of alcohol drinkers, 31.7% reported binge drinking over the last 30 days. The proportion of binge drinking was also found to be higher among males than among females. The association between current drinkers, binge drinkers and gender, area of residence, education, and family income level was statistically significant. CONCLUSIONS: This study confirms that alcohol use among current and binge drinkers is common among males in Vietnam and that it is also a rising issue among females. Alcohol use is also associated with sociodemographic factors and income level. The results of this study provide evidence of harmful alcohol use among the Vietnamese population, which could help policy makers further advocate for the approval of the Vietnamese alcohol harm reduction law in the coming years. The results of this study reaffirm the need for public health strategies, including the formulation of laws and policies to reduce the harmful effects of alcohol consumption in Vietnam.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Vigilância da População/métodos , Adolescente , Adulto , Demografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Vietnã/epidemiologia
15.
J Public Health Manag Pract ; 24 Suppl 2: S44-S51, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29369256

RESUMO

CONTEXT: Injury is a growing public health problem worldwide. Deaths due to injuries account for 10% of the world's mortality. More than 90% of the world's injury-related deaths occur in low- and middle-income countries such as Vietnam. The public health burden has been recognized by government; however, there is a need to study and better understand the epidemiology and trends for injuries and injury-related mortality to be able to better address this burden. OBJECTIVES: In this article, we analyze the patterns and trends in injury mortality from 2005 to 2013 in Vietnam. DESIGN: All registered deaths from injuries from January 2005 to December 2013 were extracted from the Ministry of Health death recording system (A6). Mortality rates per 100 000 population per year were calculated. A linear regression model was used to estimate the injury mortality trends. RESULTS: In the 9-year period, 313 101 deaths due to injuries were recorded in the A6 system; this accounts for about 10% of all deaths. The leading causes of injury-related death were road traffic injuries among the entire population, while drowning was the leading cause of death among children. Other unintentional injuries including occupational, fall, poisoning, and exposure to electric current also accounted for a substantial proportion of the burden of injury. There is a significant reduction trend found in drowning among children 0 to 18 years of age and significant increasing trends in intentional injury causes. CONCLUSIONS: While injuries have been recognized as a public health problem in Vietnam in the last decade, as seen by our analysis, there is a need for concerted action to reduce their burden. Of particular concern is the increasing prominence of intentional injuries. Improved data systems, increasing the awareness in the community, and making appropriate policies and implementing them, as well as implementing effective, evidence-based interventions are all key to decreasing this burden. This is an important study describing injury mortality in Vietnam for the period 2005-2013. The results of the study show that injury death remains an important public health issue that needs more attention from government and relevant agencies.


Assuntos
Mortalidade/tendências , Ferimentos e Lesões/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte/tendências , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Vietnã/epidemiologia , Ferimentos e Lesões/epidemiologia
17.
Aging Cell ; 23(1): e13920, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37424179

RESUMO

The geroscience hypothesis proposes that addressing the biology of aging could directly prevent the onset or mitigate the severity of multiple chronic diseases. Understanding the interplay between key aspects of the biological hallmarks of aging is essential in delivering the promises of the geroscience hypothesis. Notably, the nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several biological hallmarks of aging, including cellular senescence, and changes in NAD metabolism have been shown to be involved in the aging process. The relationship between NAD metabolism and cellular senescence appears to be complex. On the one hand, the accumulation of DNA damage and mitochondrial dysfunction induced by low NAD+ can promote the development of senescence. On the other hand, the low NAD+ state that occurs during aging may inhibit SASP development as this secretory phenotype and the development of cellular senescence are both highly metabolically demanding. However, to date, the impact of NAD+ metabolism on the progression of the cellular senescence phenotype has not been fully characterized. Therefore, to explore the implications of NAD metabolism and NAD replacement therapies, it is essential to consider their interactions with other hallmarks of aging, including cellular senescence. We propose that a comprehensive understanding of the interplay between NAD boosting strategies and senolytic agents is necessary to advance the field.


Assuntos
NAD , Nucleotídeos , NAD/metabolismo , Senescência Celular
18.
Genes (Basel) ; 15(6)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38927733

RESUMO

Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion channels have been implicated in monogenic migraine subtypes. In this study, we further examined the channelopathic nature of a migraine through the analysis of common genetic variants in three selected ion channel or transporter genes: SLC4A4, SLC1A3, and CHRNA4. Using the Agena MassARRAY platform, 28 single-nucleotide polymorphisms (SNPs) across the three candidate genes were genotyped in a case-control cohort comprised of 182 migraine cases and 179 matched controls. Initial results identified significant associations between migraine and rs3776578 (p = 0.04) and rs16903247 (p = 0.05) genotypes within the SLC1A3 gene, which encodes the EAAT1 glutamate transporter. These SNPs were subsequently genotyped in an independent cohort of 258 migraine cases and 290 controls using a high-resolution melt assay, and association testing supported the replication of initial findings-rs3776578 (p = 0.0041) and rs16903247 (p = 0.0127). The polymorphisms are in linkage disequilibrium and localise within a putative intronic enhancer region of SLC1A3. The minor alleles of both SNPs show a protective effect on migraine risk, which may be conferred via influencing the expression of SLC1A3.


Assuntos
Transportador 1 de Aminoácido Excitatório , Predisposição Genética para Doença , Transtornos de Enxaqueca , Polimorfismo de Nucleotídeo Único , Humanos , Transtornos de Enxaqueca/genética , Feminino , Masculino , Transportador 1 de Aminoácido Excitatório/genética , Adulto , Estudos de Casos e Controles , Pessoa de Meia-Idade , Estudos de Associação Genética
19.
Curr Pharm Teach Learn ; 16(10): 102151, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38996650

RESUMO

Interprofessional education is acknowledged as an efficacious strategy for fostering collaboration among healthcare professionals, especially in developing countries where interdisciplinarity and cooperation among healthcare practitioners are notably deficient. The present study aimed to investigate the readiness among medical, pharmacy, public health, and nursing faculties for development of an IPE curriculum at a university in Vietnam. Employing a quantitative approach, the revised version of the Readiness for Interprofessional Learning Scale (RIPLS) questionnaire, comprising 19 items, was utilized to gather data from sixty-nine lecturers, including 26 medicine, 23 pharmacy, 11 public health, and 9 nursing faculties. Total scores and subscores (pertaining to teamwork and collaboration, professional identity, and roles and responsibilities) were subjected to comparison using the Kruskal-Wallis and Mann-Whitney U tests. Findings revealed a high level of readiness among all faculty members toward IPE with little difference between each faculty. However, nursing lecturers exhibited a more favorable attitude toward the roles and responsibilities associated with IPE in contrast to their counterparts in the medicine faculty (1.89 ± 1.02 vs 3.15 ± 0.63, p = 0.0048). Further study with deep interview methods should be done to explore the barriers of faculty members as well as of the leadership in developing IPE.

20.
Zookeys ; 1204: 199-222, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882566

RESUMO

Molecular data from samples encompassing 22 nominal species of Poropuntius indicate that the species-level diversity in the genus has been vastly overestimated, likely due to inadequate taxon and geographic sampling and reliance on morphological characters that vary intra-specifically. The latter includes discrete mouth morphologies related to alternate feeding strategies (ecomorphs) within populations. One new species is described, Poropuntiusanlaoensis Hoàng, Pham & Tran, sp. nov., and 17 synonyms of six valid species names of Poropuntius, P.krempfi, P.alloiopleurus, P.huangchuchieni, P.laoensis, P.kontumensis, and P.deauratus, are recognised. Additional taxonomic changes in this widespread and generally poorly known genus are likely as more molecular and morphological data become available.

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