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1.
Med J Malaysia ; 79(2): 234-236, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38553931

RESUMO

Diabetes mellitus is the main aetiology of end stage kidney disease (ESKD) in Malaysia. However, there may be concerns of over-reporting of diabetes mellitus as the cause of ESKD in the Malaysian Dialysis and Transplant Registry (MDTR). The objective of this audit is to assess the accuracy of data collected in the MDTR. There were 151 centres/source data providers (SDP) with a total of 1977 patients included in this audit. The audit showed that 80.2% of doctors' records matched the MDTR data. The results were comparable with published validation studies in other countries.


Assuntos
Diabetes Mellitus , Falência Renal Crônica , Humanos , Diálise Renal/efeitos adversos , Confiabilidade dos Dados , Falência Renal Crônica/cirurgia , Sistema de Registros
2.
Med J Malaysia ; 78(6): 733-742, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38031214

RESUMO

INTRODUCTION: The incidence of acute kidney injury (AKI) among hospitalised patients has not been well studied in Malaysia. MATERIALS AND METHODS: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included. RESULTS: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17). CONCLUSION: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.


Assuntos
Injúria Renal Aguda , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Incidência , Rim , Malásia/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Idoso
3.
Am J Bot ; 109(10): 1652-1671, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36164832

RESUMO

PREMISE: Understanding evolutionary history and classifying discrete units of organisms remain overwhelming tasks, and lags in this workload concomitantly impede an accurate documentation of biodiversity and conservation management. Rapid advances and improved accessibility of sensitive high-throughput sequencing tools are fortunately quickening the resolution of morphological complexes and   thereby improving the estimation of species diversity. The recently described and critically endangered Banksia vincentia is morphologically similar to the hairpin banksia complex (B. spinulosa s.l.), a group of eastern Australian flowering shrubs whose continuum of morphological diversity has been responsible for taxonomic controversy and possibly questionable conservation initiatives. METHODS: To assist conservation while testing the current taxonomy of this group, we used high-throughput sequencing to infer a population-scale evolutionary scenario for a sample set that is comprehensive in its representation of morphological diversity and a 2500-km distribution. RESULTS: Banksia spinulosa s.l. represents two clades, each with an internal genetic structure shaped through historical separation by biogeographic barriers. This structure conflicts with the existing taxonomy for the group. Corroboration between phylogeny and population statistics aligns with the hypothesis that B. collina, B. neoanglica, and B. vincentia should not be classified as species. CONCLUSIONS: The pattern here supports how morphological diversity can be indicative of a locally expressed suite of traits rather than relationship. Oversplitting in the hairpin banksias is atypical since genomic analyses often reveal that species diversity is underestimated. However, we show that erring on overestimation can yield negative consequences, such as the disproportionate prioritization of a geographically anomalous population.


Assuntos
Proteaceae , Austrália , Filogenia , Proteaceae/genética , Evolução Biológica , Biodiversidade
4.
PLoS Pathog ; 13(12): e1006788, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29281739

RESUMO

Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, with peripheral and limb joints most commonly affected. Using a mouse model of CHIKV infection and arthritic disease, we show that CHIKV replication and the ensuing foot arthropathy were dramatically reduced when mice were housed at 30°C, rather than the conventional 22°C. The effect was not associated with a detectable fever, but was dependent on type I interferon responses. Bioinformatics analyses of RNA-Seq data after injection of poly(I:C)/jetPEI suggested the unfolded protein response and certain type I interferon responses are promoted when feet are slightly warmer. The ambient temperature thus appears able profoundly to effect anti-viral activity in the periphery, with clear consequences for alphaviral replication and the ensuing arthropathy. These observations may provide an explanation for why alphaviral arthropathies are largely restricted to joints of the limbs and the extremities.


Assuntos
Infecções por Alphavirus/imunologia , Infecções por Alphavirus/virologia , Artrite Experimental/imunologia , Artrite Experimental/virologia , Artrite Infecciosa/imunologia , Artrite Infecciosa/virologia , Interferon Tipo I/metabolismo , Infecções por Alphavirus/patologia , Animais , Artrite Experimental/patologia , Artrite Infecciosa/patologia , Febre de Chikungunya/imunologia , Febre de Chikungunya/patologia , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Vírus Chikungunya/patogenicidade , Vírus Chikungunya/fisiologia , Feminino , , Interações Hospedeiro-Patógeno/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ross River virus/imunologia , Ross River virus/patogenicidade , Ross River virus/fisiologia , Temperatura , Carga Viral , Replicação Viral/imunologia , Replicação Viral/fisiologia
5.
Neuropathol Appl Neurobiol ; 45(3): 195-215, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30298527

RESUMO

Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system (CNS) in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or CNS-specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease.


Assuntos
Doença de Alzheimer/microbiologia , Disbiose/microbiologia , Inflamação/microbiologia , Intestinos/microbiologia , Pulmão/microbiologia , Microbiota , Boca/microbiologia , Esclerose Múltipla/microbiologia , Cavidade Nasal/microbiologia , Transtornos do Olfato/microbiologia , Doença de Parkinson/microbiologia , Doença de Alzheimer/complicações , Humanos , Esclerose Múltipla/complicações , Transtornos do Olfato/etiologia , Doença de Parkinson/complicações
6.
Stem Cells ; 36(10): 1525-1534, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29873154

RESUMO

The importance of alternative splicing (AS) events in pluripotency regulation has been highlighted by the determination of different roles and contributions of different splice isoforms of pluripotency-related genes and by the identification of distinct pluripotency-related splicing factors. In particular, epithelial splicing regulatory protein 1 (ESRP1) has been characterized as an essential splicing factor required for the regulation of human pluripotency and differentiation. Nevertheless, a detailed molecular characterization of ESRP1 (mRNA splice variants 1-6) in human pluripotency is lacking. In this study, we determined that ESRP1 splice variants are differentially expressed in undifferentiated and differentiated human pluripotent stem cells (PSCs). Undifferentiated human PSCs predominantly expressed the ESRP1 v1, v4, and v5, and their expression was downregulated upon differentiation. Ectopic expression of ESRP1 v1, v4, or v5 enhanced the pluripotent reprogramming of human fibroblasts and restored the ESRP1 knockdown-mediated reduction of reprogramming efficiency. Notably, undifferentiated human PSCs expressed the cell surface protein CD44 variant 3 (CD44 v3), and isoform switching from CD44 v3 to CD44 variant 6 (CD44 v6) occurred upon differentiation. Importantly, the human PSC-specific ESRP1 variants influenced CD44 v3 expression. CD44 knockdown or inhibition of binding of CD44 with its major ligand, hyaluronan, significantly induced the loss of human PSC pluripotency and the reduction of reprogramming efficiency. Our results demonstrate that the effect of ESRP1 and CD44 on human PSC pluripotency is isoform-dependent and that ESRP1-induced CD44 v3 is functionally associated with human PSC pluripotency control. Stem Cells 2018;36:1525-1534.


Assuntos
Receptores de Hialuronatos/metabolismo , Células-Tronco Pluripotentes/metabolismo , Proteínas de Ligação a RNA/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Humanos
7.
Nanotechnology ; 30(41): 415604, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31295734

RESUMO

The development of polymer-based nanoparticulate delivery systems for siRNA is important for the clinical success of gene therapy. However, there are some major drawbacks that need to be overcome. Short interfering RNA (siRNA) has been investigated as a potential therapeutic drug to silence disease-associated genes, but its usage is limited due to the lack of effective and safe nanocarriers. In this study, DOPE-PEI, a nanoparticle consisting of the fusogenic lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) conjugated with low-molecular-weight, 600 Da, branched polyethylenimine (PEI) was produced and optimized for siRNA delivery. This delivery system was modified with other components such as 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)2000] (DOPE-PEG2K), DOPE-PEG3.4K-bombesin and 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine/1,2-dioleoyl-3-trimethylammonium-propane (DOPE/DOTAP) and tested on PC-3 cells. The conjugation of DOPE to PEI polymer (DOPE-PEI) improved the efficiency of PEI to deliver siRNA into the cytosol and knockdown genes, but demonstrated high toxicity. The addition of DOPE-PEG2K reduced cellular toxicity by masking the surface positive charge of the DOPE-PEI/siRNA complex, with the incorporation of a gastrin-releasing peptide receptor (GRPR) targeting peptide and DOPE/DOTAP components improving the cellular uptake of siRNA into targeted cells and the siRNA knockdown efficiency.


Assuntos
Nanopartículas/química , Peptídeos/química , Polímeros/química , RNA Interferente Pequeno/administração & dosagem , Linhagem Celular Tumoral , Portadores de Fármacos/química , Ácidos Graxos Monoinsaturados/química , Técnicas de Silenciamento de Genes , Técnicas de Transferência de Genes , Terapia Genética/métodos , Humanos , Iminas/química , Lipídeos/química , Células PC-3 , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Polietilenos/química , Compostos de Amônio Quaternário/química , Receptores da Bombesina/metabolismo
8.
Hong Kong Med J ; 25(5): 372-381, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31619576

RESUMO

INTRODUCTION: This study was conducted to evaluate sexual function in adult survivors of childhood cancers and investigate possible relationships between sexual function and quality of life, as measured by general well-being, self-esteem, body image, and depressive symptoms. METHODS: This cross-sectional survey was performed in our centre from 14 August 2015 to 8 September 2017. Adult patients who had a history of childhood cancers, and who were disease-free for >3 years, were approached for the study during clinical follow-up. Clinical information was collected from medical records. Self-administered questionnaires regarding quality of life and sexual functioning were given to the patients and resulting data were analysed. RESULTS: Two hundred patients agreed to participate in the study. The overall response rate was 64.8%. Ninety-one (45.5%) patients were women, and the mean age was 25.4 ± 5.57 years. The overall sexual functioning score was 28.3 ± 20.09. Forty-eight (24.0%) patients reported at least one sexual problem. Among patients who reported no sexual problems, more had haematological cancers (P=0.009), fewer underwent surgery (P=0.004), fewer underwent surgery with external effects (P=0.032), and fewer were regular social drinkers (P=0.013); additionally, they had a higher mean Rosenberg self-esteem scale score (P=0.010), lower mean body image scale score (P=0.008), and lower mean Patient Health Questionnaire score (P=0.001). CONCLUSION: Aspects of life beyond disease condition and physical function should be considered in adult survivors of childhood cancers. Appropriate referral and intervention should be initiated for these patients when necessary.


Assuntos
Sobreviventes de Câncer , Neoplasias/fisiopatologia , Neoplasias/psicologia , Qualidade de Vida , Autoimagem , Disfunções Sexuais Fisiológicas/etiologia , Adulto , Consumo de Bebidas Alcoólicas , Imagem Corporal , Criança , Estudos Transversais , Depressão , Feminino , Hong Kong , Humanos , Modelos Lineares , Masculino , Inquéritos e Questionários , Adulto Jovem
9.
Caribb J Sci ; 49(2-3): 192-200, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-32801387

RESUMO

Stressor-response research on stony corals in the laboratory relies on detecting relatively small changes in the size of coral fragments throughout the course of an experiment. Coral colonies are complex, three-dimensional (3D) communities of organisms, so small changes in size are best detected by changes in 3D surface area. Traditional methods to estimate 3D coral surface area commonly require destruction of the sample, thereby eliminating repeat measurements and the ability to calculate growth rate. However, non-destructive two-dimensional (2D) photogrammetry can be used if defensible relationships with 3D surface area can be established. In this study, 165 coral skeletons representing four stony coral species (Pocillopora damicornis, Madracis mirabilis, Orbicella faveolata, Porites porites) were photographed in 2D (top and side views) and then imaged with 3D laser scanning. Significant linear relationships were found between the 3D surface areas (laser) and the sum of various combinations of top and side view surface areas captured by 2D digital photography. The relationships were very strong for simple colony shapes and more variable as coral fragments increased in size and complexity. This study demonstrates an efficient method for obtaining estimates of 3D coral surface area from non-destructive 2D photogrammetry, allowing measurement of growth rate throughout experimental exposure periods.

10.
Pharmacogenomics J ; 17(2): 137-145, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-26856248

RESUMO

Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.


Assuntos
Processamento Alternativo , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Farmacogenética , Variantes Farmacogenômicos , Análise de Sequência de RNA , Transcriptoma , Tecido Adiposo/metabolismo , Linhagem Celular , Bases de Dados Genéticas , Genótipo , Humanos , Rim/metabolismo , Fígado/metabolismo , Miocárdio/metabolismo , Fenótipo
11.
Aust N Z J Obstet Gynaecol ; 57(2): 193-196, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28276574

RESUMO

BACKGROUND: International guidelines recommend the fallopian tubes be removed at the time of hysterectomy, to lower the incidence of ovarian cancer in women. AIMS: To determine the rate of salpingectomy at the time of hysterectomy at our institution and to discuss a standard rate. MATERIALS AND METHODS: Hysterectomies (n = 200) performed for benign indications from 13 January 13, 2015 until 26 April 26, 2016 were reviewed. RESULTS: The overall rate of salpingectomy was 76.0%. Factors associated with non-completion were uterovaginal prolapse indication and vaginal surgical approach. CONCLUSIONS: Rates of completing salpingectomy with hysterectomy are high. There may be additional opportunity for ovarian cancer reduction. No standard rate has been published but considering difficulty with removal of fallopian tubes in certain cases, it may not be 100%. Our data allows for comparison by other units performing similar studies. We recommend the formal adoption of local guidelines regarding salpingectomy at the time of hysterectomy for benign indications in order to keep local practice up to date with international recommendations.


Assuntos
Histerectomia Vaginal/estatística & dados numéricos , Salpingectomia/estatística & dados numéricos , Hemorragia Uterina/cirurgia , Prolapso Uterino/cirurgia , Adulto , Fatores Etários , Perda Sanguínea Cirúrgica , Feminino , Humanos , Histerectomia Vaginal/efeitos adversos , Complicações Intraoperatórias/etiologia , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Salpingectomia/efeitos adversos
12.
Hum Ecol ; 45(6): 809-821, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34326559

RESUMO

Ecosystem-based management involves the integration of ecosystem services and their human beneficiaries into decision making. This can occur at multiple scales; addressing global issues such as climate change down to local problems such as flood protection and maintaining water quality. At the local scale it can be challenging to achieve a consistent and sustainable outcome across multiple communities, particularly when they differ in resource availability and management priorities. A key requirement for consistent decision support at the community level is to identify common community objectives, as these can form the basis for readily transferable indices of ecosystem benefit and human well-being. We used a keyword-based approach to look for common terminology in community fundamental objectives as a basis for transferable indices of human well-being and then compared those commonalities to community demographics, location, and type. Analysis centered on strategic planning documents readily available from coastal communities in the conterminous United States. We examined strategic planning documents based on eight domains of human well-being, and found that Living Standards and Safety and Security were the most commonly addressed domains, and Health and Cultural Fulfillment were the least. In comparing communities, regional differences were observed in only one well-being domain, Safety and Security, while community type yielded significant differences in five of the eight domains examined. Community type differences followed an urban to rural trend with urban communities focusing on Education and Living Standards, and more rural communities focused on Social Cohesion and Leisure Time. Across all eight domains multivariate analysis suggested communities were distributed along two largely orthogonal gradients; one between Living Standards and Leisure Time and or Connection to Nature, and a second between Safety and Security and Social Priorities (Education/Health/Culture/Social Cohesion). Overall these findings demonstrate the use of automated keyword analysis for obtaining information from community strategic planning documents. Moreover, the results indicate measures and perceptions of well-being at the local scale differ by community type. This information could be used in management of ecosystem services and development of indices of community sustainability that are applicable to multiple communities with similar demographics, regional location, and type.

13.
Biochim Biophys Acta ; 1852(8): 1610-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25900786

RESUMO

Advanced glycation end-products (AGEs) comprise a group of non-enzymatic post-translational modifications of proteins and are elevated in diabetic tissues. AGE-modification impairs the digestibility of collagen in vitro but little is known about its relation to collagen-degrading proteinases in vivo. N(ε)-carboxymethyllysine (CML) is a stable AGE that forms on lysyl side-chains in the presence of glucose, probably via a transition metal-catalysed mechanism. Here, rats with streptozotocin-induced diabetes and non-diabetic controls were treated for 8weeks with placebo or the Cu(II)-selective chelator, triethylenetetramine (TETA), commencing 8weeks after disease induction. Actions of diabetes and drug treatment were measured on collagen and collagen-degrading proteinases in kidney tissue. The digestibility and CML content of collagen, and corresponding levels of mRNAs and collagen, were related to changes in collagen-degrading-proteinases. Collagen-degrading proteinases, cathepsin L (CTSL) and matrix metalloproteinase-2 (MMP-2) were increased in diabetic rats. CTSL-levels correlated strongly and positively with increased collagen-CML levels and inversely with decreased collagen digestibility in diabetes. The collagen-rich mesangium displayed a strong increase of CTSL in diabetes. TETA treatment normalised kidney collagen content and partially normalised levels of CML and CTSL. These data provide evidence for an adaptive proteinase response in diabetic kidneys, affected by excessive collagen-CML formation and decreased collagen digestibility. The normalisation of collagen and partial normalisation of CML- and CTSL-levels by TETA treatment supports the involvement of Cu(II) in CML formation and altered collagen metabolism in diabetic kidneys. Cu(II)-chelation by TETA may represent a treatment option to rectify collagen metabolism in diabetes independent of alterations in blood glucose levels.


Assuntos
Quelantes/metabolismo , Colágeno/metabolismo , Cobre/metabolismo , Diabetes Mellitus Experimental/metabolismo , Rim/metabolismo , Lisina/análogos & derivados , Peptídeo Hidrolases/metabolismo , Animais , Quelantes/farmacologia , Diabetes Mellitus Experimental/patologia , Rim/efeitos dos fármacos , Rim/patologia , Lisina/metabolismo , Masculino , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Wistar , Estreptozocina , Trientina/farmacologia
15.
Proc Biol Sci ; 282(1820): 20151998, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26645199

RESUMO

Seed dispersal is a key process in plant spatial dynamics. However, consistently applicable generalizations about dispersal across scales are mostly absent because of the constraints on measuring propagule dispersal distances for many species. Here, we focus on fleshy-fruited taxa, specifically taxa with large fleshy fruits and their dispersers across an entire continental rainforest biome. We compare species-level results of whole-chloroplast DNA analyses in sister taxa with large and small fruits, to regional plot-based samples (310 plots), and whole-continent patterns for the distribution of woody species with either large (more than 30 mm) or smaller fleshy fruits (1093 taxa). The pairwise genomic comparison found higher genetic distances between populations and between regions in the large-fruited species (Endiandra globosa), but higher overall diversity within the small-fruited species (Endiandra discolor). Floristic comparisons among plots confirmed lower numbers of large-fruited species in areas where more extreme rainforest contraction occurred, and re-colonization by small-fruited species readily dispersed by the available fauna. Species' distribution patterns showed that larger-fruited species had smaller geographical ranges than smaller-fruited species and locations with stable refugia (and high endemism) aligned with concentrations of large fleshy-fruited taxa, making them a potentially valuable conservation-planning indicator.


Assuntos
Frutas/anatomia & histologia , Lauraceae/anatomia & histologia , Dispersão Vegetal , Floresta Úmida , Austrália , DNA de Plantas/genética , Frutas/genética , Genoma de Cloroplastos , Genoma de Planta , Lauraceae/genética , Sementes , Análise de Sequência de DNA
16.
Hypertens Res ; 47(6): 1588-1606, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38600279

RESUMO

Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos. They have been shown to be involved in maintaining homoeostasis as well as playing a role in the development of pathology including hypertension and cardiovascular disease. It is estimated that there is 109-1010 circulating EVs/mL in the plasma of healthy individuals derived from various sources. While the effect of EVs on vascular haemodynamic parameters will be dependent on the details of the model studied, we systematically searched and summarized current literature to find patterns in how exogenously injected EVs affected vascular haemodynamics. Under homoeostatic conditions, evidence from wire and pressure myography data demonstrate that injecting isolated EVs derived from cell types found in blood and blood vessels resulted in the impairment of vasodilation in blood vessels ex vivo. Impaired vasodilation was also observed in rodents receiving intravenous injections of human plasma EVs from cardiovascular diseases including valvular heart disease, acute coronary syndrome, myocardial infarction and end stage renal disease. When EVs were derived from models of metabolic syndromes, such as diabetes, these EVs enhanced vasoconstriction responses in blood vessels ex vivo. There were fewer publications that assessed the effect of EVs in anaesthetised or conscious animals to confirm whether effects on the vasculature observed in ex vivo studies translated into alterations in vascular haemodynamics in vivo. In the available conscious animal studies, the in vivo data did not always align with the ex vivo data. This highlights the importance of in vivo work to determine the effects of EVs on the integrative vascular haemodynamics.


Assuntos
Vesículas Extracelulares , Hemodinâmica , Animais , Humanos , Doenças Cardiovasculares/fisiopatologia , Hemodinâmica/fisiologia
17.
Plants (Basel) ; 13(9)2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38732486

RESUMO

In alpine ecosystems, elevation broadly functions as a steep thermal gradient, with plant communities exposed to regular fluctuations in hot and cold temperatures. These conditions lead to selective filtering, potentially contributing to species-level variation in thermal tolerance and population-level genetic divergence. Few studies have explored the breadth of alpine plant thermal tolerances across a thermal gradient or the underlying genetic variation thereof. We measured photosystem heat (Tcrit-hot) and cold (Tcrit-cold) thresholds of ten Australian alpine species across elevation gradients and characterised their neutral genetic variation. To reveal the biogeographical drivers of present-day genetic signatures, we also reconstructed temporal changes in habitat suitability across potential distributional ranges. We found intraspecific variation in thermal thresholds, but this was not associated with elevation, nor underpinned by genetic differentiation on a local scale. Instead, regional population differentiation and considerable homozygosity within populations may, in part, be driven by distributional contractions, long-term persistence, and migrations following habitat suitability. Our habitat suitability models suggest that cool-climate-distributed alpine plants may be threatened by a warming climate. Yet, the observed wide thermal tolerances did not reflect this vulnerability. Conservation efforts should seek to understand variations in species-level thermal tolerance across alpine microclimates.

18.
Pharmacogenomics J ; 13(2): 110-20, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22231567

RESUMO

Human organic cation transporter 3 (OCT3 and SLC22A3) mediates the uptake of many important endogenous amines and basic drugs in a variety of tissues. OCT3 is identified as one of the important risk loci for prostate cancer, and is markedly underexpressed in aggressive prostate cancers. The goal of this study was to identify genetic and epigenetic factors in the promoter region that influence the expression level of OCT3. Haplotypes that contained the common variants, g.-81G>delGA (rs60515630) (minor allele frequency 11.5% in African American) and g.-2G>A (rs555754) (minor allele frequency>30% in all ethnic groups) showed significant increases in luciferase reporter activities and exhibited stronger transcription factor-binding affinity than the haplotypes that contained the major alleles. Consistent with the reporter assays, OCT3 messenger RNA expression levels were significantly higher in Asian (P<0.001) and Caucasian (P<0.05) liver samples from individuals who were homozygous for g.-2A/A in comparison with those homozygous for the g.-2G/G allele. Studies revealed that the methylation level in the basal promoter region of OCT3 was associated with OCT3 expression level and tumorigenesis capability in various prostate cancer cell lines. The methylation level of the OCT3 promoter was higher in 62% of prostate tumor samples compared with matched normal samples. Our studies demonstrate that genetic polymorphisms in the proximal promoter region of OCT3 alter the transcription rate of the gene and may be associated with altered expression levels of OCT3 in human liver. Aberrant methylation contributes to the reduced expression of OCT3 in prostate cancer.


Assuntos
Metilação de DNA/genética , Epigenômica , Proteínas de Transporte de Cátions Orgânicos/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Farmacológicos/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Etnicidade/genética , Feminino , Regulação da Expressão Gênica , Frequência do Gene , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
19.
Eur J Cancer Care (Engl) ; 22(4): 440-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23374018

RESUMO

The purpose of this study was to survey the current state of oncology sperm banking services provided by fertility clinics across Canada. A total of 78 Canadian fertility facilities were invited to complete a questionnaire related to the availability, accessibility, affordability and utilisation of sperm banking services for cancer patients. The total response rate was 59%, with 20 (69%) in vitro fertilisation clinics and 26 (53%) other fertility centres returning the survey. A total of 24 responding facilities accepted oncology sperm banking referrals. The time frame to book the first banking appointment for 19 (79%) facilities was within 2 days. Inconsistent practice was found regarding the consent process for cancer patients who are of minority age. Eight (33%) facilities did not provide any subsidy and charged a standard banking fee regardless of patients' financial situations. Overall, the utilisation of oncology sperm banking services was low despite its availability and established efficacy, suggesting that Canadian cancer patients are notably underserved. The study has highlighted some important issues for further consideration in improving access to sperm banking services for cancer patients, especially for adolescents. Better collaboration between oncology and reproductive medicine to target healthcare providers would help to improve sperm banking rates.


Assuntos
Acessibilidade aos Serviços de Saúde/normas , Neoplasias , Bancos de Esperma/estatística & dados numéricos , Adolescente , Adulto , Canadá , Custos de Cuidados de Saúde , Humanos , Consentimento Livre e Esclarecido/normas , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Bancos de Esperma/economia , Bancos de Esperma/provisão & distribuição , Inquéritos e Questionários , Adulto Jovem
20.
Invest Ophthalmol Vis Sci ; 64(15): 18, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38099736

RESUMO

Purpose: The purpose of this study was to assess the immediate ocular immune response to soft contact lens (CL) wear by examining presumed epithelial immune cell (EIC) density and morphology at the central, peripheral, limbal cornea, and conjunctiva. Methods: Fifty-four participants naïve to CL wear (mean age = 24.8 ± 9.8 years, 44% female participants), were examined using in vivo confocal microscopy at baseline and after 2 hours of CL wear (1-Day ACUVUE MOIST). Images were captured at the central, temporal far peripheral and limbal cornea, and bulbar conjunctiva. EIC density was counted manually and morphology was graded. Differences in EIC parameters pre- and post-CL wear were examined using a generalized estimating equation model with appropriate post hoc analyses. Results: After 2 hours of soft CL wear, there was a significant increase in EIC density in all regions other than the central cornea (all P < 0.001). Cell body size was significantly larger, and a higher proportion of participants exhibited EIC with long dendrites after lens wear at the central and peripheral cornea (both P < 0.001). There was a significant increase in the number of participants displaying EIC with thick dendrites at the peripheral (P = 0.04) and limbal cornea (P < 0.001) after lens wear. Conclusions: EICs were primarily recruited to the peripheral regions, whereas the central cornea shows no significant recruitment after short-term CL wear. Both central and peripheral corneas exhibited an enhanced antigen capture capacity, whereas migratory capacity was increased in the peripheral corneal regions suggesting EIC activation following a short period of CL wear.


Assuntos
Lentes de Contato Hidrofílicas , Células Epiteliais , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Masculino , Epitélio , Córnea , Apresentação de Antígeno
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