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1.
Pest Manag Sci ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888426

RESUMO

BACKGROUND: The mechanisms that regulate multi-annual population dynamics of rodent pest species of cereal crops is often unknown. Better knowledge of such aspects can aid pest management and in turn improve food security and human health. The patterns and processes of the population dynamics of Rattus argentiventer, in rice fields of Indonesia, and Rattus tanezumi, in rice fields of the Philippines were assessed in this article. RESULTS: The meta-analysis of trapping data over 20 years in Indonesia, and 16 years in the Philippines indicated that rodent populations in rice fields did not show a regular multi-annual pattern. Rattus argentiventer populations in Indonesia responded to less rainfall from the current year. Rattus tanezumi populations in the Philippines responded positively to both rainfall and rainfall anomaly with a 1-year time lag. CONCLUSIONS: Our study of long-term population data indicates that certain combinations of rainfall parameters could be useful to predict years when there is higher rodent abundance in rice fields. The key rodent pest species in rice fields in Indonesia (R. argentiventer) and the Philippines (R. tanezumi) differ, and the populations of each species respond differently to rainfall anomalies. Other factors such as crop cover and water availability may also be important and should be considered in future work. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

2.
Environ Sci Pollut Res Int ; 30(7): 16984-17008, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36622585

RESUMO

A small proportion of the thousands of pesticides on the market today are associated with a disproportionately high incidence of severe acute pesticide poisoning and suicide. Paraquat stands out as one of the most lethal pesticides in common use, frequently involved in fatal incidents due to suicides or accidental exposure. Even though paraquat has been banned in over 67 countries, it is still widely used in many others, particularly in Asia and Latin America. Based on a literature review and consultations, this paper identifies options for replacing paraquat and distils practical lessons from numerous successes around the world. Our aim is to support regulators, policymakers, agronomists and the supply chain sector with practical information related to phasing out paraquat. Production data consistently failed to show any negative effects of banning paraquat on agricultural productivity. A wide range of alternative approaches to weed management and crop defoliation are available, many of which do not rely on herbicides. Over 1.25 million farmers in low- and middle-income countries (LMICs) successfully produce a range of crops for private voluntary standards (PVS) in food and fiber supply chains which prohibit paraquat use. We conclude from the findings of this study that eliminating paraquat will save lives without reducing agricultural productivity. Less hazardous and more sustainable alternatives exist. To enhance successful adoption and uptake of these methods on a wide scale, farmers require training and support within an enabling policy environment.


Assuntos
Herbicidas , Praguicidas , Suicídio , Humanos , Paraquat , Agricultura
3.
Nat Commun ; 13(1): 5202, 2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057633

RESUMO

Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination of the translation factor EIF5A (EIF5AH). Here, we have found that hepatic DOHH mRNA expression is decreased in patients and mice with non-alcoholic steatohepatitis (NASH), and hepatic cells treated with fatty acids. The mouse and cell culture models of NASH have concomitant decreases in Eif5aH and mitochondrial protein synthesis which leads to lower mitochondrial activity and fatty acid ß-oxidation. Spermidine treatment restores EIF5AH, partially restores protein synthesis and mitochondrial function in NASH, and prevents NASH progression in vivo. Thus, the disrupted DHPS-DOHH-EIF5AH pathway during NASH represents a therapeutic target to increase hepatic protein synthesis and mitochondrial fatty acid oxidation (FAO) and prevent NASH progression.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Espermidina , Animais , Ácidos Graxos , Lisina/metabolismo , Camundongos , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Espermidina/farmacologia
4.
J Hepatol ; 77(5): 1246-1255, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35820507

RESUMO

BACKGROUND & AIMS: Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH. METHODS: We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B12 (B12) and folate (Fol) to reverse NASH features in mice and cell culture. RESULTS: Serum Hcy correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was downregulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to a block in autophagy. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B12/Fol, which promotes enzymatic conversion of Hcy to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated ß -oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH. CONCLUSIONS: HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B12/folate also may represent a novel first-line therapy for NASH. LAY SUMMARY: The incidence of non-alcoholic steatohepatitis, for which there are no approved pharmacological therapies, is increasing, posing a significant healthcare challenge. Herein, based on studies in mice, primates and humans, we found that dietary supplementation with vitamin B12 and folate could have therapeutic potential for the prevention or treatment of non-alcoholic steatohepatitis.


Assuntos
Hiper-Homocisteinemia , Hepatopatia Gordurosa não Alcoólica , Animais , Ácidos Graxos , Fibrose , Ácido Fólico , Homocisteína , Humanos , Inflamação , Metionina , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Proteínas Qa-SNARE , Vitamina B 12 , Vitaminas
5.
Pest Manag Sci ; 78(10): 4252-4260, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35711128

RESUMO

BACKGROUND: Trapping is a key method for monitoring small mammals and is also one of a number of methods recommended under an ecologically-based rodent management program to control rodent pest populations. Live-traps are widely used globally for studying small mammal populations. In Asia where rodents are major pests of rice, single capture traps typically provide low trap success. We compared the trap success between two types of live-traps in rice fields in Indonesia and the Philippines. RESULTS: Multiple-capture traps (MCTs) in conjunction with a linear trap barrier were significantly more effective in catching rodent pest species than single-capture traps (SCTs) in Indonesia and the Philippines. In Indonesia, MCTs captured more individuals with a mean (±SE) percent trap success rate of (15.54 ± 4.29) compared to SCTs (3.88 ± 1.58). In the Philippines, MCTs captured more species of rodents and had a significantly higher recapture rate (1.96 ± 0.79), than SCTs (0.58 ± 0.32). CONCLUSION: Multiple-capture traps with a linear trap-barrier were more effective for capturing Rattus argentiventer and Rattus tanezumi in rice field ecosystems compared to single-capture traps. MCTs captured more species of rodent pests in the Philippines and recaptured more individuals of each species. These results indicate that rodent populations can be more effectively monitored and controlled by using a multi-capture trap with barrier system than the use of single capture traps on their own. This is the first time these two trap types have been compared for use in rice ecosystems in Asia. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Ecossistema , Oryza , Animais , Controle de Pragas , Ratos , Roedores , Sigmodontinae
6.
Eur J Neurosci ; 56(9): 5476-5515, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35510513

RESUMO

The APOE gene encoding the Apolipoprotein E protein is the single most significant genetic risk factor for late-onset Alzheimer's disease. The APOE4 genotype confers a significantly increased risk relative to the other two common genotypes APOE3 and APOE2. Intriguingly, APOE4 has been associated with neuropathological and cognitive deficits in the absence of Alzheimer's disease-related amyloid or tau pathology. Here, we review the extensive literature surrounding the impact of APOE genotype on central nervous system dysfunction, focussing on preclinical model systems and comparison of APOE3 and APOE4, given the low global prevalence of APOE2. A multi-hit hypothesis is proposed to explain how APOE4 shifts cerebral physiology towards pathophysiology through interconnected hits. These hits include the following: neurodegeneration, neurovascular dysfunction, neuroinflammation, oxidative stress, endosomal trafficking impairments, lipid and cellular metabolism disruption, impaired calcium homeostasis and altered transcriptional regulation. The hits, individually and in combination, leave the APOE4 brain in a vulnerable state where further cumulative insults will exacerbate degeneration and lead to cognitive deficits in the absence of Alzheimer's disease pathology and also a state in which such pathology may more easily take hold. We conclude that current evidence supports an APOE4 multi-hit hypothesis, which contributes to an APOE4 pathophysiological state. We highlight key areas where further study is required to elucidate the complex interplay between these individual mechanisms and downstream consequences, helping to frame the current landscape of existing APOE-centric literature.


Assuntos
Doença de Alzheimer , Apolipoproteína E4 , Humanos , Doença de Alzheimer/metabolismo , Apolipoproteína E2/genética , Apolipoproteína E2/metabolismo , Apolipoproteína E3/genética , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo
7.
Thyroid ; 32(6): 725-738, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35317606

RESUMO

Background: Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, lobular inflammation, and fibrosis. Thyroid hormone (TH) reduces steatosis; however, the therapeutic effect of TH on NASH-associated inflammation and fibrosis is not known. This study examined the therapeutic effect of TH on hepatic inflammation and fibrosis during NASH and investigated THs molecular actions on autophagy and mitochondrial biogenesis. Methods: HepG2-TRß cells were treated with bovine serum albumin-conjugated palmitic acid (PA) to mimic lipotoxic conditions in vitro. Mice with NASH were established by feeding C57BL/6J mice Western diet with 15% fructose in drinking water for 16 weeks. These mice were administered triiodothyronine (T3)/thyroxine (T4) supplemented in drinking water for the next eight weeks. Results: In cultured HepG2-TRß cells, TH treatment increased mitochondrial respiration and fatty acid oxidation under basal and PA-treated conditions, as well as decreased lipopolysaccharides and PA-stimulated inflammatory and fibrotic responses. In a dietary mouse model of NASH, TH administration decreased hepatic triglyceride content (3.19 ± 0.68 vs. 8.04 ± 0.42 mM/g liver) and hydroxyproline (1.44 ± 0.07 vs. 2.58 ± 0.30 mg/g liver) when compared with mice with untreated NASH. Metabolomics profiling of lipid metabolites showed that mice with NASH had increased triacylglycerol, diacylglycerol, monoacylglycerol, and hepatic cholesterol esters species, and these lipid species were decreased by TH treatment. Mice with NASH also showed decreased autophagic degradation as evidenced by decreased transcription Factor EB and lysosomal protease expression, and accumulation of LC3B-II and p62. TH treatment restored the level of lysosomal proteins and resolved the accumulation of LC3B-II and p62. Impaired mitochondrial biogenesis was also restored by TH. The simultaneous restoration of autophagy and mitochondrial biogenesis by TH increased ß-oxidation of fatty acids. Additionally, the elevated oxidative stress and inflammasome activation in NASH liver were also decreased by TH. Conclusions: In a mouse model of NASH, TH restored autophagy and mitochondrial biogenesis to increase ß-oxidation of fatty acids and to reduce lipotoxicity, oxidative stress, hepatic inflammation, and fibrosis. Activating thyroid hormone receptor in the liver may represent an effective strategy for NASH treatment.


Assuntos
Água Potável , Hepatopatia Gordurosa não Alcoólica , Animais , Modelos Animais de Doenças , Água Potável/metabolismo , Ácidos Graxos/metabolismo , Fibrose , Humanos , Inflamação/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hormônios Tireóideos/metabolismo , Triglicerídeos/metabolismo
8.
Sci Rep ; 12(1): 401, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013482

RESUMO

Overuse of seed and chemical inputs is a major constraint for sustainable rice production in Vietnam. In this study, two seasons of field trials were conducted to compare different crop establishment practices for rice production in the Mekong River Delta using environmental and economic sustainability performance indicators. The indicators including energy efficiency, agronomic use efficiency, net income, and greenhouse gas emissions (GHGEs) were quantified based on four treatments including manual broadcast-seeding, blower seeding, drum seeding, and mechanized transplanting. Across the four treatments, yields ranged from 7.3-7.5 Mg ha-1 and 6.2-6.8 Mg ha-1 in the Winter-Spring (WS) and Summer-Autumn (SA) seasons, respectively. In comparison with direct seeding methods, mechanized transplanting decreased the seed rate by 40%. It also led to a 30-40% reduction in pesticide use during the main crop season (WS). Mechanized transplanting required higher inputs, including machine depreciation and fuel consumption, but its net energy balance, net income and GHGE were at a similar level as the other non-mechanized planting practices. Mechanized transplanting is a technology package that should be promoted to improve the economic and environmental sustainability of lowland rice cultivation in the Mekong River Delta of Vietnam.

9.
Nat Food ; 3(3): 217-226, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-37117641

RESUMO

Southeast Asia is a major rice-producing region with a high level of internal consumption and accounting for 40% of global rice exports. Limited land resources, climate change and yield stagnation during recent years have once again raised concerns about the capacity of the region to remain as a large net exporter. Here we use a modelling approach to map rice yield gaps and assess production potential and net exports by 2040. We find that the average yield gap represents 48% of the yield potential estimate for the region, but there are substantial differences among countries. Exploitable yield gaps are relatively large in Cambodia, Myanmar, Philippines and Thailand but comparably smaller in Indonesia and Vietnam. Continuation of current yield trends will not allow Indonesia and Philippines to meet their domestic rice demand. In contrast, closing the exploitable yield gap by half would drastically reduce the need for rice imports with an aggregated annual rice surplus of 54 million tons available for export. Our study provides insights for increasing regional production on existing cropland by narrowing existing yield gaps.

10.
Integr Zool ; 17(6): 1017-1027, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34695302

RESUMO

The rice field rat, Rattus argentiventer, is a significant pest of rice in Southeast Asia. Fertility control methods have the potential to provide safe and effective alternatives to control methods that often include indiscriminate use of rodenticides or electric barriers. The aim of this laboratory study was to assess uptake of bait coated with different concentrations of the contraceptive hormones, quinestrol (E) and levonorgestrel (P), delivered alone and in combination (i.e. EP-1) and determine the short-term effects on reproductive parameters of adult male and female R. argentiventer. In Experiment 1, 2 concentrations of E, P, and EP-1 (10, 20 ppm) were fed to groups of wild-caught rats for 7 days. In females, both E and EP-1 induced uterine edema. In males, EP-1 reduced epididymis and seminal vesicle weights and lowered sperm motility. However, these responses were inconsistent due to low bait acceptance, especially with increasing concentrations. In Experiment 2, EP-1 (0, 20, 50, 100 ppm) was administered by oral gavage daily for 7 days to male R. argentiventer. There were significant reductions in epididymal and seminal vesicle weights for all oral doses of EP-1, in sperm counts for the 50 ppm dose, and in sperm motility for the 20 and 50 ppm doses compared to the control group. To select the optimum dose of EP-1, we must address the poor acceptance of contraceptive-coated baits by rice field rats. Further research is required to improve the palatability of EP-1 and to test its uptake under field conditions.


Assuntos
Oryza , Quinestrol , Masculino , Feminino , Ratos , Animais , Quinestrol/farmacologia , Motilidade dos Espermatozoides , Anticoncepcionais/farmacologia , Sigmodontinae , Tamanho do Órgão , Sementes , Hormônios/farmacologia
11.
Nat Commun ; 12(1): 7163, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34887412

RESUMO

Future rice systems must produce more grain while minimizing the negative environmental impacts. A key question is how to orient agricultural research & development (R&D) programs at national to global scales to maximize the return on investment. Here we assess yield gap and resource-use efficiency (including water, pesticides, nitrogen, labor, energy, and associated global warming potential) across 32 rice cropping systems covering half of global rice harvested area. We show that achieving high yields and high resource-use efficiencies are not conflicting goals. Most cropping systems have room for increasing yield, resource-use efficiency, or both. In aggregate, current total rice production could be increased by 32%, and excess nitrogen almost eliminated, by focusing on a relatively small number of cropping systems with either large yield gaps or poor resource-use efficiencies. This study provides essential strategic insight on yield gap and resource-use efficiency for prioritizing national and global agricultural R&D investments to ensure adequate rice supply while minimizing negative environmental impact in coming decades.

13.
Pest Manag Sci ; 77(10): 4249-4261, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33949075

RESUMO

Rodents present a major problem for food security in Asia where smallholder farming families are particularly vulnerable. We review here recent developments in the biology and management of rodent pests in cereal cropping systems in Asia. The past decade has seen a strong focus on ecologically-based rodent management (EBRM), its adoption in field studies significantly increased rice yields (6-15%) and income (>15%) in seven Asian countries. EBRM principles have also been successfully applied to maize in China. We provide case studies on EBRM in Cambodia, on interactions between rodent pests and weeds, and on the importance of modified wetlands for biodiversity and rodent pest management. Knowledge on post-harvest impacts of rodents is increasing. One research gap is the assessment of human health impacts from a reduction of rodent densities in and around houses. We identify 10 challenges for the next decade. For example, the need for population modelling, a valuable tool missing from our toolbox to manage rodent pests in cereal systems. We also need to understand better the interactive effects of cropping intensification, conservation agriculture and climate change. Finally, new management approaches such as fertility control are on the horizon and need to be considered in the context of smallholder cereal farming systems and mitigating health risks from zoonotic diseases associated with rodents. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Grão Comestível , Roedores , Agricultura , Animais , Ásia , Segurança Alimentar
14.
Genome Med ; 13(1): 3, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413596

RESUMO

BACKGROUND: Family history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards genomics-first approaches in population screening programs rendering the value of family history unknown. We evaluated the utility of incorporating family history information for genomic sequencing selection. METHODS: To ascertain the relationship between family histories on such population-level initiatives, we analysed whole genome sequences of 1750 research participants with no known pre-existing conditions, of which half received comprehensive family history assessment of up to four generations, focusing on 95 cancer genes. RESULTS: Amongst the 1750 participants, 866 (49.5%) had high-quality standardised family history available. Within this group, 73 (8.4%) participants had an increased family history risk of cancer (increased FH risk cohort) and 1 in 7 participants (n = 10/73) carried a clinically actionable variant inferring a sixfold increase compared with 1 in 47 participants (n = 17/793) assessed at average family history cancer risk (average FH risk cohort) (p = 0.00001) and a sevenfold increase compared to 1 in 52 participants (n = 17/884) where family history was not available (FH not available cohort) (p = 0.00001). The enrichment was further pronounced (up to 18-fold) when assessing only the 25 cancer genes in the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes. Furthermore, 63 (7.3%) participants had an increased family history cancer risk in the absence of an apparent clinically actionable variant. CONCLUSIONS: These findings demonstrate that the collection and analysis of comprehensive family history and genomic data are complementary and in combination can prioritise individuals for genomic analysis. Thus, family history remains a critical component of health risk assessment, providing important actionable data when implementing genomics screening programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02791152 . Retrospectively registered on May 31, 2016.


Assuntos
Atenção à Saúde , Genômica , Anamnese , Medicina de Precisão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
15.
Front Cardiovasc Med ; 8: 816985, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35242820

RESUMO

BACKGROUND: The quantitative measures used to assess the performance of automated methods often do not reflect the clinical acceptability of contouring. A quality-based assessment of automated cardiac magnetic resonance (CMR) segmentation more relevant to clinical practice is therefore needed. OBJECTIVE: We propose a new method for assessing the quality of machine learning (ML) outputs. We evaluate the clinical utility of the proposed method as it is employed to systematically analyse the quality of an automated contouring algorithm. METHODS: A dataset of short-axis (SAX) cine CMR images from a clinically heterogeneous population (n = 217) were manually contoured by a team of experienced investigators. On the same images we derived automated contours using a ML algorithm. A contour quality scoring application randomly presented manual and automated contours to four blinded clinicians, who were asked to assign a quality score from a predefined rubric. Firstly, we analyzed the distribution of quality scores between the two contouring methods across all clinicians. Secondly, we analyzed the interobserver reliability between the raters. Finally, we examined whether there was a variation in scores based on the type of contour, SAX slice level, and underlying disease. RESULTS: The overall distribution of scores between the two methods was significantly different, with automated contours scoring better than the manual (OR (95% CI) = 1.17 (1.07-1.28), p = 0.001; n = 9401). There was substantial scoring agreement between raters for each contouring method independently, albeit it was significantly better for automated segmentation (automated: AC2 = 0.940, 95% CI, 0.937-0.943 vs manual: AC2 = 0.934, 95% CI, 0.931-0.937; p = 0.006). Next, the analysis of quality scores based on different factors was performed. Our approach helped identify trends patterns of lower segmentation quality as observed for left ventricle epicardial and basal contours with both methods. Similarly, significant differences in quality between the two methods were also found in dilated cardiomyopathy and hypertension. CONCLUSIONS: Our results confirm the ability of our systematic scoring analysis to determine the clinical acceptability of automated contours. This approach focused on the contours' clinical utility could ultimately improve clinicians' confidence in artificial intelligence and its acceptability in the clinical workflow.

16.
J Cardiovasc Magn Reson ; 22(1): 10, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008575

RESUMO

OBJECTIVES: The imaging features of dilated cardiomyopathy (DCM) overlap with physiological exercise-induced cardiac remodeling in active and otherwise healthy individuals. Distinguishing the two conditions is challenging. This study examined the diagnostic and prognostic roles of exercise stress imaging in asymptomatic patients with suspected DCM. METHODS: Exercise stress cardiovascular magnetic resonance (CMR) was performed in 60 asymptomatic patients with suspected DCM (dilated left ventricle and/or impaired systolic function on CMR), who also underwent DNA sequencing for DCM-causing genetic variants. Confirmed DCM was defined as genotype- and phenotype-positive (G+P+). Another 100 healthy subjects were recruited to establish normal exercise capacities (peak exercise cardiac index; PeakCI). The primary outcome was a composite of all-cause mortality, cardiac decompensation and ventricular arrhythmic events. RESULTS: No patients with confirmed G+P+ DCM had PeakCI exceeding the 35th percentile specific for age and sex. Applying this threshold in G-P+ patients, those with PeakCI below 35th percentile had characteristics similar to confirmed DCM while patients with higher PeakCI were younger, more active and higher longitudinal strain. Adverse cardiovascular events occurred only in patients with low exercise capacity (P = 0.004). CONCLUSIONS: In individuals with suspected DCM, exercise stress CMR demonstrates diagnostic and prognostic potential in distinguishing between pathological DCM and physiological exercise-induced cardiac remodeling.


Assuntos
Cardiomegalia Induzida por Exercícios , Cardiomiopatia Dilatada/diagnóstico por imagem , Teste de Esforço , Imagem Cinética por Ressonância Magnética , Adulto , Doenças Assintomáticas , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Causas de Morte , Diagnóstico Diferencial , Progressão da Doença , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Volume Sistólico , Função Ventricular Esquerda , Adulto Jovem
17.
PLoS One ; 15(1): e0227505, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31917819

RESUMO

Interleukin 11 (IL11) is a profibrotic cytokine, secreted by myofibroblasts and damaged epithelial cells. Smooth muscle cells (SMCs) also secrete IL11 under pathological conditions and express the IL11 receptor. Here we examined the effects of SMC-specific, conditional expression of murine IL11 in a transgenic mouse (Il11SMC). Within days of transgene activation, Il11SMC mice developed loose stools and progressive bleeding and rectal prolapse, which was associated with a 65% mortality by two weeks. The bowel of Il11SMC mice was inflamed, fibrotic and had a thickened wall, which was accompanied by activation of ERK and STAT3. In other organs, including the heart, lung, liver, kidney and skin there was a phenotypic spectrum of fibro-inflammation, together with consistent ERK activation. To investigate further the importance of stromal-derived IL11 in the inflammatory bowel phenotype we used a second model with fibroblast-specific expression of IL11, the Il11Fib mouse. This additional model largely phenocopied the Il11SMC bowel phenotype. These data show that IL11 secretion from the stromal niche is sufficient to drive inflammatory bowel disease in mice. Given that IL11 expression in colonic stromal cells predicts anti-TNF therapy failure in patients with ulcerative colitis or Crohn's disease, we suggest IL11 as a therapeutic target for inflammatory bowel disease.


Assuntos
Fibroblastos/patologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Interleucina-11/genética , Fenótipo , Animais , Colo/patologia , Progressão da Doença , Fibrose , Expressão Gênica , Masculino , Camundongos , Camundongos Transgênicos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia
18.
BMC Cardiovasc Disord ; 19(1): 259, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752689

RESUMO

BACKGROUND: Cardiovascular disease (CVD) imposes much mortality and morbidity worldwide. The use of "deep learning", advancements in genomics, metabolomics, proteomics and devices like wearables have the potential to unearth new insights in the field of cardiology. Currently, in Asia, there are no studies that combine the use of conventional clinical information with these advanced technologies. We aim to harness these new technologies to understand the development of cardiovascular disease in Asia. METHODS: Singapore is a multi-ethnic country in Asia with well-represented diverse ethnicities including Chinese, Malays and Indians. The SingHEART study is the first technology driven multi-ethnic prospective population-based study of healthy Asians. Healthy male and female subjects aged 21-69 years old without any prior cardiovascular disease or diabetes mellitus will be recruited from the general population. All subjects are consented to undergo a detailed on-line questionnaire, basic blood investigations, resting and continuous electrocardiogram and blood pressure monitoring, activity and sleep tracking, calcium score, cardiac magnetic resonance imaging, whole genome sequencing and lipidomic analysis. Outcomes studied will include mortality and cause of mortality, myocardial infarction, stroke, malignancy, heart failure, and the development of co-morbidities. DISCUSSION: An initial target of 2500 patients has been set. From October 2015 to May 2017, an initial 683 subjects have been recruited and have completed the initial work-up the SingHEART project is the first contemporary population-based study in Asia that will include whole genome sequencing and deep phenotyping: including advanced imaging and wearable data, to better understand the development of cardiovascular disease across different ethnic groups in Asia.


Assuntos
Povo Asiático/genética , Doenças Cardiovasculares/genética , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Nível de Saúde , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Singapura/epidemiologia , Sequenciamento Completo do Genoma , Adulto Jovem
19.
Insects ; 10(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581452

RESUMO

Integrated biodiversity management aims to conserve the beneficial species components of production ecosystems and reduce the impacts of pests. In 2011 and 2013, experiments were conducted at Los Baños, Laguna, Philippines, to compare arthropod communities in rice plots and on levees with and without vegetation strips. Vegetation strips included spontaneous weeds, sesame and okra (2011), or mung bean (2013). The plots were treated with one of three nitrogen levels and in one experiment were planted with planthopper-resistant (IR62) and susceptible (IR64) rice varieties. Parasitoids and predators of lepidopteran pests and of the ricebug, Leptocorisa oratorius, were more abundant in high-nitrogen rice plots where their prey/hosts also had highest densities. Planthoppers and leafhoppers were more abundant in low-nitrogen plots. Weedy and sesame/okra bunds provided habitat for a range of natural enemies including spiders, parasitoids and predatory bugs, but did not have higher pest numbers than cleared bunds. Higher abundances of the predator Cythorhinus lividipennis and higher parasitism of planthopper (Nilaparvata lugens) eggs by Anagrus sp. were associated with sesame/okra bunds in late season rice plots. Mung bean also provided habitat for key predators and parasitoids that spilled over to adjacent rice; however, mung bean was also associated with higher numbers of lepidopteran and grain-sucking pests in the adjacent rice, albeit without increased damage to the rice. For ricebug in particular, damage was probably reduced by higher parasitoid:pest ratios adjacent to the vegetation strips. Varietal resistance and mung bean strips had an additive effect in reducing abundance of the planthopper Sogatella furcifera and the leafhopper Nephotettix virescens. Reduced numbers of these latter pests close to vegetation strips were often compensated for by other plant-sucking bugs, thereby increasing the intensity of potentially stabilizing interspecific interactions such as competition. We highlight the benefits of diversifying rice landscapes and the need to optimize vegetation strips, e.g., by including lepidopteran trap-plants, for intensive rice production systems.

20.
Commun Biol ; 2: 361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602410

RESUMO

Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST; they included age, gender, occupation and alcohol consumption. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with cardiovascular disease risk markers such as body mass index and waist circumference, whereas self-reported measures were not. Using wearable-derived TST, we showed that insufficient sleep was associated with premature telomere attrition. Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.


Assuntos
Envelhecimento , Doenças Cardiovasculares/epidemiologia , Sono , Adulto , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Autorrelato , Telômero , Circunferência da Cintura , Dispositivos Eletrônicos Vestíveis , Adulto Jovem
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