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1.
Heliyon ; 10(13): e33462, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39027486

RESUMEN

This study examines the intellectual framework research in bank lending and technological innovation relationships in countries with high banking system liquidity. This study employs bibliometrics with R-studio tools and procedures to analyze documents regarding productions, collaborations, keyword occurrences, conceptual structure, and density and centrality occurrence's network. Combining data from the Web of Science and Scopus databases, this study obtained 939 documents from 527 sources with a significant opportunity for further elevation through combination with other themes. The development analysis based on the most related countries indicates that researchers from other countries have also conducted studies identified as having significant banking liquidity. Topic development and thematic evolution show that research on the role of bank lending on technological innovation evolves to environmental issues, with green credit as the most recent and emerging elaboration. For further direction, keywords in investment clusters can help elevate education, commerce, and impact clusters by combining them with research on government taxation, credit provision, sustainable development, and emission control themes.

2.
J Am Coll Cardiol ; 84(5): 434-446, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39048275

RESUMEN

BACKGROUND: Accurate risk stratification is vital for primary prevention of cardiovascular disease (CVD). However, traditional tools such as the Framingham Risk Score (FRS) may underperform within the diverse intermediate-risk group, which includes individuals requiring distinct management strategies. OBJECTIVES: This study aimed to develop a lipidomic-enhanced risk score (LRS), specifically targeting risk prediction and reclassification within the intermediate group, benchmarked against the FRS. METHODS: The LRS was developed via a machine learning workflow using ridge regression on the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab; n = 10,339). It was externally validated with the Busselton Health Study (n = 4,492), and its predictive utility for coronary artery calcium scoring (CACS)-based outcomes was independently validated in the BioHEART cohort (n = 994). RESULTS: LRS significantly improved discrimination metrics for the intermediate-risk group in both AusDiab and Busselton Health Study cohorts (all P < 0.001), increasing the area under the curve for CVD events by 0.114 (95% CI: 0.1123-0.1157) and 0.077 (95% CI: 0.0755-0.0785), with a net reclassification improvement of 0.36 (95% CI: 0.21-0.51) and 0.33 (95% CI: 0.15-0.49), respectively. For CACS-based outcomes in BioHEART, LRS achieved a significant area under the curve improvement of 0.02 over the FRS (0.76 vs 0.74; P < 1.0 × 10-5). A simplified, clinically applicable version of LRS was also created that had comparable performance to the original LRS. CONCLUSIONS: LRS, augmenting the FRS, presents potential to improve intermediate-risk stratification and to predict atherosclerotic markers using a simple blood test, suitable for clinical application. This could facilitate the triage of individuals for noninvasive imaging such as CACS, fostering precision medicine in CVD prevention and management.


Asunto(s)
Enfermedades Cardiovasculares , Prevención Primaria , Humanos , Prevención Primaria/métodos , Medición de Riesgo/métodos , Femenino , Enfermedades Cardiovasculares/prevención & control , Persona de Mediana Edad , Masculino , Lipidómica/métodos , Anciano , Factores de Riesgo de Enfermedad Cardiaca , Australia/epidemiología , Aprendizaje Automático , Adulto
3.
Diabetes Res Clin Pract ; 216: 111795, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39084293

RESUMEN

AIMS: To quantify rates of dementia treatment and death among Australians with type 2 diabetes relative to those without diabetes using linked national registries of Australia. METHODS: The study included 891,418 people with type 2 diabetes registered on the National Diabetes Services Scheme and a randomly sampled, population-based comparison group (n = 1,131,369). Outcomes included dementia death (all-cause dementia, Alzheimer's disease (AD) or vascular dementia), and first prescription of cholinesterase inhibitors or memantine. RESULTS: Excess dementia risk was observed in the diabetes group for the composite outcome of all-cause dementia death or dementia medication prescription but varied with age at diabetes diagnosis and its duration. At age 70, the rate of dementia death/medication prescription was ∼1.3 (95% CI 1.2, 1.3) and 1.1 (95% CI 1.1, 1.2) times higher in people with ten and five years of diabetes duration, respectively. Individual outcomes showed that diabetes was associated with a higher incidence of vascular dementia death, whereas an increased risk of AD death was only observed beyond âˆ¼10 years of diabetes duration. Further, the incidence of dementia medication prescription was lower among people with diabetes. CONCLUSIONS: A higher incidence of AD death in the setting of 10+ years of diabetes duration coupled with a lower incidence of AD treatment suggests an under-recognition of this dementia phenotype among people with type 2 diabetes.


Asunto(s)
Demencia , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Demencia/epidemiología , Demencia/mortalidad , Demencia/tratamiento farmacológico , Anciano , Australia/epidemiología , Incidencia , Persona de Mediana Edad , Anciano de 80 o más Años , Memantina/uso terapéutico , Inhibidores de la Colinesterasa/uso terapéutico , Sistema de Registros
4.
Diabetes Care ; 47(8): 1457-1462, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38916200

RESUMEN

OBJECTIVE: To estimate the relative risk (RR) and excess hospitalization rate for injury in individuals with diabetes compared with the general population. RESEARCH DESIGN AND METHODS: Data were obtained from the Australian National Diabetes Services Scheme, hospitalization data sets, the Australian Pharmaceutical Benefits Scheme, the National Death Index, and the census spanning from 2011 to 2017. Hospitalizations for injury were coded as head and neck, lower-extremity, upper-extremity, or abdominal and thoracic injury; burns; or other injury. Poisson regression was used to estimate the age- and sex-adjusted RR of hospitalization for injury. RESULTS: The total number of hospitalizations for any injury was 117,705 in people with diabetes and 3,463,173 in the general population. Compared with that in the general population, an elevated adjusted risk of admission was observed for any injury (RR 1.22; 95% CI 1.21, 1.22), head and neck (1.28; 1.26, 1.30), lower extremity (1.24; 1.23, 1.26), abdominal and thoracic (1.29; 1.27, 1.30), upper extremity (1.03; 1.02, 1.05), burns (1.52; 1.44, 1.61), and other injury (1.37; 1.33, 1.40). The adjusted RR of any injury was 1.62 (1.58, 1.66) in individuals with type 1 diabetes, 1.65 (1.63, 1.66) in those with type 2 diabetes who were taking insulin, and 1.07 (1.06, 1.08) in individuals with type 2 diabetes not using insulin. Falls were the primary cause of injury in individuals with diabetes. CONCLUSIONS: Individuals with diabetes, especially those using insulin, had a higher risk of hospitalization for injury compared with the general population.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hospitalización , Heridas y Lesiones , Humanos , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Hospitalización/estadística & datos numéricos , Adolescente , Adulto Joven , Heridas y Lesiones/epidemiología , Niño , Australia/epidemiología , Preescolar , Anciano de 80 o más Años , Lactante
5.
EBioMedicine ; 105: 105199, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38905750

RESUMEN

BACKGROUND: Metabolic ageing biomarkers may capture the age-related shifts in metabolism, offering a precise representation of an individual's overall metabolic health. METHODS: Utilising comprehensive lipidomic datasets from two large independent population cohorts in Australia (n = 14,833, including 6630 males, 8203 females), we employed different machine learning models, to predict age, and calculated metabolic age scores (mAge). Furthermore, we defined the difference between mAge and age, termed mAgeΔ, which allow us to identify individuals sharing similar age but differing in their metabolic health status. FINDINGS: Upon stratification of the population into quintiles by mAgeΔ, we observed that participants in the top quintile group (Q5) were more likely to have cardiovascular disease (OR = 2.13, 95% CI = 1.62-2.83), had a 2.01-fold increased risk of 12-year incident cardiovascular events (HR = 2.01, 95% CI = 1.45-2.57), and a 1.56-fold increased risk of 17-year all-cause mortality (HR = 1.56, 95% CI = 1.34-1.79), relative to the individuals in the bottom quintile group (Q1). Survival analysis further revealed that men in the Q5 group faced the challenge of reaching a median survival rate due to cardiovascular events more than six years earlier and reaching a median survival rate due to all-cause mortality more than four years earlier than men in the Q1 group. INTERPRETATION: Our findings demonstrate that the mAge score captures age-related metabolic changes, predicts health outcomes, and has the potential to identify individuals at increased risk of metabolic diseases. FUNDING: The specific funding of this article is provided in the acknowledgements section.


Asunto(s)
Biomarcadores , Factores de Riesgo Cardiometabólico , Enfermedades Cardiovasculares , Lipidómica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Lipidómica/métodos , Anciano , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Adulto , Envejecimiento/metabolismo , Australia/epidemiología , Factores de Edad , Factores de Riesgo , Medición de Riesgo/métodos
6.
Genome Biol ; 25(1): 99, 2024 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637899

RESUMEN

Spatial molecular data has transformed the study of disease microenvironments, though, larger datasets pose an analytics challenge prompting the direct adoption of single-cell RNA-sequencing tools including normalization methods. Here, we demonstrate that library size is associated with tissue structure and that normalizing these effects out using commonly applied scRNA-seq normalization methods will negatively affect spatial domain identification. Spatial data should not be specifically corrected for library size prior to analysis, and algorithms designed for scRNA-seq data should be adopted with caution.


Asunto(s)
Perfilación de la Expresión Génica , Análisis de la Célula Individual , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Perfilación de la Expresión Génica/métodos , Algoritmos , Biología
7.
Am J Kidney Dis ; 84(1): 8-17.e1, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38551531

RESUMEN

RATIONALE & OBJECTIVE: Evidence has demonstrated that albuminuria is a key diagnostic and prognostic marker of diabetic chronic kidney disease, but the impact of its day-to-day variability has not been adequately considered. This study quantified within-individual variability of albuminuria in people with type 2 diabetes to inform clinical albuminuria monitoring. STUDY DESIGN: Descriptive cross-sectional analysis. SETTING & PARTICIPANTS: People with type 2 diabetes (n=826, 67.1 [IQR, 60.3-72.4] years, 64.9% male) participating in the Progression of Diabetic Complications (PREDICT) cohort study. EXPOSURE: Four spot urine collections for measurement of urinary albumin-creatinine ratio (UACR) within 4 weeks. OUTCOME: Variability of UACR. ANALYTICAL APPROACH: We characterized within-individual variability (coefficient of variation [CV], 95% limits of random variation, intraclass correlation coefficient), developed a calculator displaying probabilities that any observed difference between a pair of UACR values truly exceeded a 30% difference, and estimated the ranges of diagnostic uncertainty to inform a need for additional UACR collections to exclude or confirm albuminuria. Multiple linear regression examined factors influencing UACR variability. RESULTS: We observed high within-individual variability (CV 48.8%; 95% limits of random variation showed a repeated UACR to be as high/low as 3.78/0.26 times the first). If a single-collection UACR increased from 2 to 5mg/mmol, the probability that UACR actually increased by at least 30% was only 50%, rising to 97% when 2 collections were obtained at each time point. The ranges of diagnostic uncertainty were 2.0-4.0mg/mmol after an initial UACR test, narrowing to 2.4-3.2 and 2.7-2.9mg/mmol for the mean of 2 and 3 collections, respectively. Some factors correlated with higher (female sex; moderately increased albuminuria) or lower (reduced estimated glomerular filtration rate and sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment) within-individual UACR variability. LIMITATIONS: Reliance on the mean of 4 UACR collections as the reference standard for albuminuria. CONCLUSIONS: UACR demonstrates a high degree of within-individual variability among individuals with type 2 diabetes. Multiple urine collections for UACR may improve capacity to monitor changes over time in clinical and research settings but may not be necessary for the diagnosis of albuminuria. PLAIN-LANGUAGE SUMMARY: Albuminuria (albumin in urine) is a diagnostic and prognostic marker of diabetic chronic kidney disease. However, albuminuria can vary within an individual from day to day. We compared 4 random spot urinary albumin-creatinine ratio (UACR) samples from 826 participants. We found that a second UACR collection may be as small as a fourth or as large as almost 4 times the first sample's UACR level. This high degree of variability presents a challenge to our ability to interpret changes in albuminuria. Multiple collections have been suggested as a solution. We have constructed tools that may aid clinicians in deciding how many urine collections are required to monitor and diagnose albuminuria. Multiple urine collections may be required for individual monitoring but not necessarily for diagnosis.


Asunto(s)
Albuminuria , Creatinina , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/orina , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Albuminuria/orina , Albuminuria/diagnóstico , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Creatinina/orina , Anciano , Nefropatías Diabéticas/orina , Nefropatías Diabéticas/diagnóstico , Estudios de Cohortes
8.
Liver Int ; 44(2): 508-517, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38010999

RESUMEN

BACKGROUND AND AIMS: The burden of liver disease among people with diabetes at a population level is unknown. We explored the burden and trends of liver disease mortality and hospitalisations among Australians with diabetes. METHODS: We linked Australians with type 2 diabetes on the National Diabetes Services Scheme to the National Death Index for 2002-2019 to determine trends in the proportion of deaths due to liver disease, overall and by subcategory. We also determined the leading reasons and risk factors for liver disease hospitalisations in those with diabetes over this period. Finally, we compared the burden of liver disease hospitalisations among those with diabetes to the general population using excess hospitalisations per 100 000 person-years. RESULTS: Among Australians with type 2 diabetes (n = 1 122 431) liver diseases accounted for between 1.5% and 1.9% of deaths between 2002 and 2019, roughly one-third of the proportion of deaths caused by kidney disease. The proportion of deaths due to inflammatory liver diseases among those with diabetes increased from .08% in 2002 to .27% in 2019. Alcohol-related liver disease accounted for the greatest share (22.7%) of liver disease hospitalisation in those with diabetes, but the number of hospitalisations for this condition declined over time. Compared to the general population, men (RR 3.63, 95% CI 3.44-3.84) and women (RR 4.49, 4.21-4.78) with diabetes were at higher risk of hospitalisation for fibrosis and cirrhosis; however, this did not translate to a substantial excess risk per 100 000 population. CONCLUSIONS: Better screening methods for liver disease among people with diabetes should be developed and implemented into practice.


Asunto(s)
Pueblos de Australasia , Diabetes Mellitus Tipo 2 , Hepatopatías , Masculino , Humanos , Femenino , Diabetes Mellitus Tipo 2/epidemiología , Australia/epidemiología , Hospitalización
9.
Genome Biol ; 24(1): 209, 2023 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-37723583

RESUMEN

Identifying spatially variable genes (SVGs) is a key step in the analysis of spatially resolved transcriptomics data. SVGs provide biological insights by defining transcriptomic differences within tissues, which was previously unachievable using RNA-sequencing technologies. However, the increasing number of published tools designed to define SVG sets currently lack benchmarking methods to accurately assess performance. This study compares results of 6 purpose-built packages for SVG identification across 9 public and 5 simulated datasets and highlights discrepancies between results. Additional tools for generation of simulated data and development of benchmarking methods are required to improve methods for identifying SVGs.


Asunto(s)
Benchmarking , Transcriptoma , Perfilación de la Expresión Génica
10.
Blood Adv ; 7(21): 6506-6519, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37567157

RESUMEN

Hematopoiesis produces diverse blood cell lineages to meet the basal needs and sudden demands of injury or infection. A rapid response to such challenges requires the expansion of specific lineages and a prompt return to balanced steady-state levels, necessitating tightly coordinated regulation. Previously we identified a requirement for the zinc finger and broad complex, tramtrak, bric-a-brac domain-containing 11 (ZBTB11) transcription factor in definitive hematopoiesis using a forward genetic screen for zebrafish myeloid mutants. To understand its relevance to mammalian systems, we extended these studies to mice. When Zbtb11 was deleted in the hematopoietic compartment, embryos died at embryonic day (E) 18.5 with hematopoietic failure. Zbtb11 hematopoietic knockout (Zbtb11hKO) hematopoietic stem cells (HSCs) were overabundantly specified from E14.5 to E17.5 compared with those in controls. Overspecification was accompanied by loss of stemness, inability to differentiate into committed progenitors and mature lineages in the fetal liver, failure to seed fetal bone marrow, and total hematopoietic failure. The Zbtb11hKO HSCs did not proliferate in vitro and were constrained in cell cycle progression, demonstrating the cell-intrinsic role of Zbtb11 in proliferation and cell cycle regulation in mammalian HSCs. Single-cell RNA sequencing analysis identified that Zbtb11-deficient HSCs were underrepresented in an erythroid-primed subpopulation and showed downregulation of oxidative phosphorylation pathways and dysregulation of genes associated with the hematopoietic niche. We identified a cell-intrinsic requirement for Zbtb11-mediated gene regulatory networks in sustaining a pool of maturation-capable HSCs and progenitor cells.


Asunto(s)
Células Madre Hematopoyéticas , Pez Cebra , Animales , Ratones , Regulación de la Expresión Génica , Hematopoyesis/genética , Células Madre Hematopoyéticas/metabolismo , Mamíferos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Pez Cebra/metabolismo
11.
Commun Biol ; 6(1): 804, 2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37532769

RESUMEN

RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.


Asunto(s)
Genética de Población , Humanos , Estudios Retrospectivos , Genotipo , Secuencia de Bases , Análisis de Secuencia de ARN
12.
Heliyon ; 9(7): e18229, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37519658

RESUMEN

Using a novel panel data set we study the influence of monetary and macro-prudential policies on non-performing loans as a measure of credit risk in Indonesian banking industry from Q1 2010 to Q4 2022. The panel homogeneity assumption was verified through the utilization of the Chow and Roy-Zellner tests. The findings showed that the model was not homogenous, necessitating the use of the Pooled Mean Group (PMG) estimator. The results indicated that monetary and macro-prudential policies significantly impacted credit risk. Furthermore, tight monetary and macro-prudential policies increased and reduced credit risk in the long run, respectively. The findings also showed that a loosening monetary policy reduced credit risk in the short run. Therefore, higher authorities must establish effective monetary and macro-prudential policies to reduce the non-performing loan ratio and maintain credit risk in Indonesia's banking industry.

13.
Body Image ; 46: 117-122, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37290141

RESUMEN

This project aimed to establish whether meaningful body image profiles (BIPs) could be identified across measures of body shame, body appreciation, and body mass index (BMI), and whether these profiles could differentiate key health behaviours. Data came from 1200 adult women who responded to an online body image survey. Latent profile analysis was used to identify BIPs based on relative levels of body shame, body appreciation and BMI. Differences in dietary restraint and weekly exercise amount were investigated according to BIP membership. Latent profile analysis revealed four unique BIPs; 1. Appreciative BIP (AP-BIP); 2. Medium Shame BIP (MS-BIP); 3. High Shame BIP (HS-BIP) and 4. Average BIP (AV-BIP). Dietary restraint and exercise amount differed significantly according to BIP in most comparisons. Women in the High Shame BIP exhibited the highest dietary restraint and lowest exercise. Women in the Appreciative BIP exhibited the lowest dietary restraint and highest exercise. Body shame and body appreciation intersect with BMI to form unique profiles (BIPs) that differentiate dietary restraint and exercise. Using BIPs to tailor interventions designed to promote healthful diet and exercise should be considered in public health initiatives.


Asunto(s)
Imagen Corporal , Dieta , Adulto , Humanos , Femenino , Índice de Masa Corporal , Imagen Corporal/psicología , Ejercicio Físico , Vergüenza
14.
Commun Biol ; 6(1): 265, 2023 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-36914713

RESUMEN

Atherosclerotic plaque rupture leading to myocardial infarction is a major global health burden. Applying the tandem stenosis (TS) mouse model, which distinctively exhibits the characteristics of human plaque instability/rupture, we use quantitative proteomics to understand and directly compare unstable and stable atherosclerosis. Our data highlight the disparate natures and define unique protein signatures of unstable and stable atherosclerosis. Key proteins and pathway networks are identified such as the innate immune system, and neutrophil degranulation. The latter includes calprotectin S100A8/A9, which we validate in mouse and human unstable plaques, and we demonstrate the plaque-stabilizing effects of its inhibition. Overall, we provide critical insights into the unique proteomic landscape of unstable atherosclerosis (as distinct from stable atherosclerosis and vascular tissue). We further establish the TS model as a reliable preclinical tool for the discovery and testing of plaque-stabilizing drugs. Finally, we provide a knowledge resource defining unstable atherosclerosis that will facilitate the identification and validation of long-sought-after therapeutic targets and drugs for plaque stabilization.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Humanos , Animales , Ratones , Placa Aterosclerótica/tratamiento farmacológico , Proteómica , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética , Aterosclerosis/metabolismo , Modelos Animales de Enfermedad
15.
Diabetes Res Clin Pract ; 196: 110244, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36632938

RESUMEN

AIMS: To determine the burden and leading reasons for mental health hospitalisation among Australians with diabetes. METHODS: We determined the incidence of hospitalisation for all mental health disorders in people with type 1 or type 2 diabetes of all ages by linking the National Diabetes Services Scheme to hospital admission datasets from 2010 to 2017. We compared those with type 2 diabetes aged 15 and above to the general population using excess hospitalisations per 100,000 person-years associated with diabetes. RESULTS: Depressive disorders were the leading reason for mental health admission in Australians with diabetes, responsible for 6.09 (95% CI 5.78-6.42) and 7.05 (6.95-7.14) admissions per 1,000 person-years in those with type 1 and type 2 diabetes, respectively. When considering only one admission per person, mental health admission rates were up to 90% lower. Among males with type 2 diabetes, stress and adjustment disorders were the leading cause of excess admissions compared to the general population, while depressive disorders were the leading cause in females. CONCLUSIONS: We found a substantial burden of psychiatric hospitalisations among Australians with diabetes, reinforcing the importance of mental health awareness among diabetes clinicians, and support by psychiatric teams for those with diabetes to prevent readmission.


Asunto(s)
Diabetes Mellitus Tipo 2 , Trastornos Mentales , Masculino , Femenino , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Salud Mental , Australia , Hospitalización
16.
Mol Biol Cell ; 34(3): ar13, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36598812

RESUMEN

Rho GTPases regulate cell morphogenesis and motility under the tight control of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). However, the underlying mechanism(s) that coordinate their spatiotemporal activities, whether separately or together, remain unclear. We show that a prometastatic RhoGAP, ARHGAP8/BPGAP1, binds to inactive Rac1 and localizes to lamellipodia. BPGAP1 recruits the RacGEF Vav1 under epidermal growth factor (EGF) stimulation and activates Rac1, leading to polarized cell motility, spreading, invadopodium formation, and cell extravasation and promotes cancer cell migration. Importantly, BPGAP1 down-regulates local RhoA activity, which influences Rac1 binding to BPGAP1 and its subsequent activation by Vav1. Our results highlight the importance of BPGAP1 in recruiting Vav1 and Rac1 to promote Rac1 activation for cell motility. BPGAP1 also serves to control the timing of Rac1 activation with RhoA inactivation via its RhoGAP activity. BPGAP1, therefore, acts as a dual-function scaffold that recruits Vav1 to activate Rac1 while inactivating RhoA to synchronize both Rho and Rac signaling in cell motility. As epidermal growth factor receptor (EGFR), Vav1, RhoA, Rac1, and BPGAP1 are all associated with cancer metastasis, BPGAP1 could provide a crucial checkpoint for the EGFR-BPGAP1-Vav1-Rac1-RhoA signaling axis for cancer intervention.


Asunto(s)
Movimiento Celular , Proteínas Activadoras de GTPasa , Humanos , Secuencia de Aminoácidos , Receptores ErbB/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Proteínas de Unión al GTP rho/metabolismo
17.
Circulation ; 147(7): 532-545, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36342348

RESUMEN

BACKGROUND: Breast cancer survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 patients with early-stage breast cancer scheduled for AC to determine whether 12 months of exercise training (ExT) could attenuate functional disability (primary end point), improve cardiorespiratory fitness (VO2peak), and prevent cardiac dysfunction. METHODS: Women 40 to 75 years of age with stage I to III breast cancer scheduled for AC were randomized to 3 to 4 days per week aerobic and resistance ExT for 12 months (n=52) or usual care (UC; n=52). Functional measures were performed at baseline, at 4 weeks after AC (4 months), and at 12 months, comprising: (1) cardiopulmonary exercise testing to quantify VO2peak and functional disability (VO2peak ≤18.0 mL·kg-1·min-1); (2) cardiac reserve (response from rest to peak exercise), quantified with exercise cardiac magnetic resonance measures to determine changes in left and right ventricular ejection fraction, cardiac output, and stroke volume; (3) standard-of-care echocardiography-derived resting left ventricular ejection fraction and global longitudinal strain; and (4) biochemistry (troponin and BNP [B-type natriuretic peptide]). RESULTS: Among 104 participants randomized, greater study attrition was observed among UC participants (P=0.031), with 93 women assessed at 4 months (ExT, n=49; UC, n=44) and 87 women assessed at 12 months (ExT, n=49; UC, n=38). ExT attenuated functional disability at 4 months (odds ratio, 0.32 [95% CI, 0.11-0.94]; P=0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06-1.12]; P=0.07). In a per-protocol analysis, functional disability was prevented entirely at 12 months among participants adherent to ExT (ExT, 0% versus UC, 20%; P=0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL·kg-1·min-1 improvement in VO2peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve (P<0.001 for all). There was no effect of ExT on resting measures of left ventricular function. Postchemotherapy troponin increased less in ExT than in UC (8-fold versus 16-fold increase; P=0.002). There were no changes in BNP in either group. CONCLUSIONS: In women with early-stage breast cancer undergoing AC, 12 months of ExT did not attenuate functional disability, but provided large, clinically meaningful benefits on VO2peak and cardiac reserve. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12617001408370.


Asunto(s)
Neoplasias de la Mama , Cardiopatías , Humanos , Femenino , Recién Nacido , Volumen Sistólico , Antraciclinas/efectos adversos , Función Ventricular Izquierda , Unión Europea , Cardiotoxicidad/prevención & control , Cardiotoxicidad/etiología , Reino Unido , Función Ventricular Derecha , Cardiopatías/diagnóstico por imagen , Cardiopatías/prevención & control , Antibióticos Antineoplásicos/farmacología , Ejercicio Físico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Troponina
18.
Sci Rep ; 12(1): 22236, 2022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-36564466

RESUMEN

Varying technologies and experimental approaches used in microbiome studies often lead to irreproducible results due to unwanted technical variations. Such variations, often unaccounted for and of unknown source, may interfere with true biological signals, resulting in misleading biological conclusions. In this work, we aim to characterize the major sources of technical variations in microbiome data and demonstrate how in-silico approaches can minimize their impact. We analyzed 184 pig faecal metagenomes encompassing 21 specific combinations of deliberately introduced factors of technical and biological variations. Using the novel Removing Unwanted Variations-III-Negative Binomial (RUV-III-NB), we identified several known experimental factors, specifically storage conditions and freeze-thaw cycles, as likely major sources of unwanted variation in metagenomes. We also observed that these unwanted technical variations do not affect taxa uniformly, with freezing samples affecting taxa of class Bacteroidia the most, for example. Additionally, we benchmarked the performances of different correction methods, including ComBat, ComBat-seq, RUVg, RUVs, and RUV-III-NB. While RUV-III-NB performed consistently robust across our sensitivity and specificity metrics, most other methods did not remove unwanted variations optimally. Our analyses suggest that a careful consideration of possible technical confounders is critical during experimental design of microbiome studies, and that the inclusion of technical replicates is necessary to efficiently remove unwanted variations computationally.


Asunto(s)
Microbiota , Animales , Porcinos , Microbiota/genética , Metagenoma , Congelación , Bacteroidetes , Heces
19.
BMC Public Health ; 22(1): 2218, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36447213

RESUMEN

BACKGROUND: Bodily pain is a common presentation in several chronic diseases, yet the influence of sedentary behaviour, common in ageing adults, is unclear. Television-viewing (TV) time is a ubiquitous leisure-time sedentary behaviour, with a potential contribution to the development of bodily pain. We examined bodily pain trajectories and the longitudinal relationships of TV time with the bodily pain severity; and further, the potential moderation of the relationships by type 2 diabetes (T2D) status. METHOD: Data were from 4099 participants (aged 35 to 65 years at baseline) in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), who took part in the follow-ups at 5 years, 12 years, or both. Bodily pain (from SF36 questionnaire: a 0 to 100 scale, where lower scores indicate more-severe pain), TV time, and T2D status [normal glucose metabolism (NGM), prediabetes, and T2D] were assessed at all three time points. Multilevel growth curve modelling used age (centred at 50 years) as the time metric, adjusting for potential confounders, including physical activity and waist circumference. RESULTS: Mean TV time increased, and bodily pain worsened (i.e., mean bodily pain score decreased) across the three time points. Those with T2D had higher TV time and more-severe bodily pain than those without T2D at all time points. In a fully adjusted model, the mean bodily pain score for those aged 50 years at baseline was 76.9(SE: 2.2) and worsened (i.e., bodily pain score decreased) significantly by 0.3(SE: 0.03) units every additional year (p <0.001). Those with initially more-severe pain had a higher rate of increase in pain severity. At any given time point, a one-hour increase in daily TV time was significantly associated with an increase in pain severity [bodily pain score decreased by 0.69 (SE: 0.17) units each additional hour; p <0.001], accounting for the growth factor (age) and confounders' effects. The association was more-pronounced in those with T2D than in those without (prediabetes or NGM), with the effect of T2D on bodily pain severity becoming more apparent as TV time increases, significantly so when TV time increased above 2.5 hours per day. CONCLUSION: Bodily pain severity increased with age in middle-aged and older Australian adults over a 12-year period, and increments in TV time predicted increased bodily pain severity at any given period, which was more pronounced in those with T2D. While increasing physical activity is a mainstay of the prevention and management of chronic health problems, these new findings highlight the potential of reducing sedentary behaviours in this context.


Asunto(s)
Diabetes Mellitus Tipo 2 , Estado Prediabético , Adulto , Persona de Mediana Edad , Humanos , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Estudios Prospectivos , Australia/epidemiología , Dolor/epidemiología , Televisión
20.
Diabetes Res Clin Pract ; 194: 110143, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36370894

RESUMEN

AIMS: We sought to quantify the burden and diversity of reasons for hospital admission amongst Australians with type 2 diabetes compared to the general population. METHODS: We linked Australians aged 15 and above with type 2 diabetes on the National Diabetes Services Scheme (n = 456,265) to hospital admission data to determine hospitalisation risks at ICD-10 three-digit diagnosis level for 2010-2017. We performed Poisson regression to determine the hospitalisation burden of each diagnosis among those with diabetes compared to the general population and reported excess annual hospitalisations per 100,000 people with diabetes. RESULTS: Australians with diabetes were at increased risk of hospitalisation for most conditions. In addition to traditional complications including heart failure, other conditions such as mental health disorders and anaemias were major causes for excess hospitalisation, compared to the general population. The leading cause of excess hospitalisation in women with diabetes was iron deficiency anaemia, responsible for 558 excess annual hospitalisations per 100,000 women with diabetes. In men, the leading cause was cellulitis, responsible for 364 excess annual hospitalisations per 100,000. CONCLUSIONS: The diseases responsible for excess hospitalisations in type 2 diabetes are more diverse than previously recognised. This may need to be reflected in changes to diabetes management.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Trastornos Mentales , Masculino , Humanos , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Australia/epidemiología , Hospitalización , Insuficiencia Cardíaca/complicaciones , Trastornos Mentales/complicaciones
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