ABSTRACT
OBJECTIVE: Dizziness or vertigo in older population frequently presents in clinical settings, yet its etiology remains elusive. The objective of this study was to delineate global trends and identify frontiers in research concerning dizziness or vertigo among older population. METHODS: We searched the research literature published from 2003 to 2022 on older population with dizziness or vertigo using two databases from the Web of Science Core Collection. A bibliometric and visualization analysis was conducted. Bibliometric tools facilitated co-authorship, co-citation, and keyword co-occurrence analyses, encompassing countries or regions, institutions, authors, journals, and references. RESULTS: The analysis included 1322 publications authored by 6524 individuals from 2244 institutions across 67 countries or regions, spanning 92 subject categories. A steady increase in publications was noted from 2003 to 2022. The University of Munich, Harvard University, and the University of California System emerged as leading institutions with the highest publication outputs. The United States, Germany, and China were predominant in publication counts. Eva Grill was identified as the most prolific author. Otology & Neurotology and Geriatrics & Gerontology emerged as the most prolific journal and subject category, respectively. The most prevalent keywords were "dizziness", "vertigo", "falls", and "geriatric", with "management", "gait", and "association" recognized as the principal research hotspots. CONCLUSION: This study provides a systematic analysis of global scientific research on older population dizziness/vertigo, revealing significant advancements in understanding over the past two decades. Management, gait, and association have emerged as the primary research focuses on recent years. These findings offer valuable insights for directing current research efforts to capture prevailing trends and explore new frontiers in this field.
Subject(s)
Bibliometrics , Dizziness , Vertigo , Humans , Aged , Global Health , Biomedical Research/trends , Biomedical Research/statistics & numerical dataABSTRACT
Alzheimer's Disease (AD) continues to be a leading cause of death in the US. As the US aging population (ages 65 +) expands, the impact will disproportionately affect vulnerable populations, e.g., Hispanic/Latino population, due to their AD-related health disparities. Age-related regression in mitochondrial activity and ethnic-specific differences in metabolic burden could potentially explain in part the racial/ethnic distinctions in etiology that exist for AD. Oxidation of guanine (G) to 8-oxo-guanine (8oxoG) is a prevalent lesion and an indicator of oxidative stress and mitochondrial dysfunction. Damaged mtDNA (8oxoG) can serve as an important marker of age-related systemic metabolic dysfunction and upon release into peripheral circulation may exacerbate pathophysiology contributing to AD development and/or progression. Analyzing blood samples from Mexican American (MA) and non-Hispanic White (NHW) participants enrolled in the Texas Alzheimer's Research & Care Consortium, we used blood-based measurements of 8oxoG from both buffy coat PBMCs and plasma to determine associations with population, sex, type-2 diabetes, and AD risk. Our results show that 8oxoG levels in both buffy coat and plasma were significantly associated with population, sex, years of education, and reveal a potential association with AD. Furthermore, MAs are significantly burdened by mtDNA oxidative damage in both blood fractions, which may contribute to their metabolic vulnerability to developing AD.
Subject(s)
Alzheimer Disease , DNA Damage , DNA, Mitochondrial , Mitochondria , Oxidative Stress , Aged , Humans , Alzheimer Disease/genetics , DNA, Mitochondrial/genetics , Guanine , Mexican Americans/genetics , Mitochondria/genetics , Oxidative Stress/genetics , DNA Damage/genetics , White/geneticsABSTRACT
BACKGROUND: Peritoneal metastasis (PM) is an important factor contributing to poor prognosis in patients with gastric cancer (GC). Transcriptomic sequencing has been used to explore the molecular changes in metastatic cancers, but comparing the bulk RNA-sequencing data between primary tumors and metastases in PM studies is unreasonable due to the small proportion of tumor cells in PM tissues. METHODS: We performed single-cell RNA-sequencing analysis on four gastric adenocarcinoma specimens, including one primary tumor sample (PT), one adjacent nontumoral sample (PN), one peritoneal metastatic sample (MT) and one normal peritoneum sample (MN), from the same patient. Pseudotime trajectory analysis was used to display the process by which nonmalignant epithelial cells transform into tumor cells and then metastasize to the peritoneum. Finally, in vitro and in vivo assays were used to validate one of the selected genes that promote peritoneal metastasis. RESULTS: Single-cell RNA sequencing showed that a development curve was found from normal mucosa to tumor tissues and then into metastatic sites on peritoneum. TAGLN2 was found to trigger this metastasis process. The migration and invasion capability of GC cells were changed by downregulating and upregulating TAGLN2 expression. Mechanistically, TAGLN2 might modulate tumor metastasis via alterations in cell morphology and several signaling pathways, thus promoting epithelial-mesenchymal transition (EMT). CONCLUSIONS: In summary, we identified and validated TAGLN2 as a novel gene involved in GC peritoneal metastasis. This study provided valuable insight into the mechanisms of GC metastasis and developed a potential therapeutic target to prevent GC cell dissemination.
Subject(s)
Peritoneal Neoplasms , Stomach Neoplasms , Humans , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial Cells/pathology , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Peritoneal Neoplasms/genetics , Peritoneum , RNA , Stomach Neoplasms/pathology , Up-RegulationABSTRACT
Alzheimer's Disease (AD) continues to be a leading cause of death in the US. As the US aging population (ages 65+) expands, the impact will disproportionately affect vulnerable populations, e.g., Hispanic/Latinx population, due to their AD-related health disparities. Age-related regression in mitochondrial activity and ethnic-specific differences in metabolic burden could potentially explain in part the racial/ethnic distinctions in etiology that exist for AD. Oxidation of guanine (G) to 8-oxo-guanine (8oxoG) is a prevalent lesion and an indicator of oxidative stress and mitochondrial dysfunction. Damaged mtDNA (8oxoG) can serve as an important marker of age-related systemic metabolic dysfunction and upon release into peripheral circulation may exacerbate pathophysiology contributing to AD development and/or progression. Analyzing blood samples from Mexican American (MA) and non-Hispanic White (NHW) participants enrolled in the Texas Alzheimer's Research & Care Consortium, we used blood-based measurements of 8oxoG from both buffy coat PBMCs and plasma to determine associations with population, sex, type-2 diabetes, and AD risk. Our results show that 8oxoG levels in both buffy coat and plasma were significantly associated with population, sex, years of education, and reveal a potential association with AD. Furthermore, MAs are significantly burdened by mtDNA oxidative damage in both blood fractions, which may contribute to their metabolic vulnerability to developing AD.
ABSTRACT
BACKGROUND: The aging Mexican American (MA) population is the fastest growing ethnic minority group in the US. MAs have a unique metabolic-related risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI), compared to non-Hispanic whites (NHW). This risk for cognitive impairment (CI) is multifactorial involving genetics, environmental, and lifestyle factors. Changes in environment and lifestyle can alter patterns and even possibly reverse derangement of DNA methylation (a form of epigenetic regulation). OBJECTIVE: We sought to identify ethnicity-specific DNA methylation profiles that may be associated with CI in MAs and NHWs. METHODS: DNA obtained from peripheral blood of 551 participants from the Texas Alzheimer's Research and Care Consortium was typed on the Illumina Infinium® MethylationEPIC chip array, which assesses over 850K CpG genomic sites. Within each ethnic group (Nâ=â299 MAs, Nâ=â252 NHWs), participants were stratified by cognitive status (control versus CI). Beta values, representing relative degree of methylation, were normalized using the Beta MIxture Quantile dilation method and assessed for differential methylation using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages in R. RESULTS: Two differentially methylated sites were significant: cg13135255 (MAs) and cg27002303 (NHWs) based on an FDR pâ<â0.05. Three suggestive sites obtained were cg01887506 (MAs) and cg10607142 and cg13529380 (NHWs). Most methylation sites were hypermethylated in CI compared to controls, except cg13529380 which was hypomethylated. CONCLUSION: The strongest association with CI was at cg13135255 (FDR-adjusted pâ=â0.029 in MAs), within the CREBBP gene. Moving forward, identifying additional ethnicity-specific methylation sites may be useful to discern CI risk in MAs.
Subject(s)
CREB-Binding Protein , Cognitive Dysfunction , DNA Methylation , Mexican Americans , White , Aged , Humans , Cognitive Dysfunction/blood , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/ethnology , Cognitive Dysfunction/genetics , CREB-Binding Protein/blood , CREB-Binding Protein/genetics , DNA Methylation/genetics , Epigenesis, Genetic/genetics , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/ethnology , Genetic Predisposition to Disease/genetics , Mexican Americans/genetics , Minority Groups , Risk Factors , White/geneticsABSTRACT
Mexican Americans (MAs) are the fastest-growing Hispanic population segment in the US; as this population increases in age, so will the societal burden of age-related diseases such as Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be implicated in MA AD risk since metabolic comorbidities are more prevalent in this group. Oxidative damage to guanosine (8oxoG) is one of the most prevalent DNA lesions and a putative indicator of mitochondrial dysfunction. Testing blood samples from participants of the Texas Alzheimer's Research and Care Consortium, we found mtDNA 8oxoG mutational load to be significantly higher in MAs compared to non-Hispanic whites and that MA females are differentially affected. Furthermore, we identified specific mtDNA haplotypes that confer increased risk for oxidative damage and suggestive evidence that cognitive function may be related to 8oxoG burden. Our understanding of these phenomena will elucidate population- and sex-specific mechanisms of AD pathogenesis, informing the development of more precise interventions and therapeutic approaches for MAs with AD in the future.
Subject(s)
Atrial Fibrillation , Heart Failure , Hip Fractures , Aged , Heart Failure/surgery , Hip Fractures/surgery , Humans , Risk FactorsABSTRACT
ABSTRACT With the gradual improvement of people's quality of life, the average life expectancy of our country has been extended. It is estimated that the total number of the elderly population in China will exceed 250 million by the end of 2020. Therefore, promoting healthy aging is a necessary measure to cope with the coming aging society in China, and physical exercise is an important method to keep the physical and mental health of the elderly. In order to promote the development of healthy aging in China, this study focused on the current level of public sports services for the elderly. This study uses the expert consultation method to test the rationality of the evaluation index, and uses the method of questionnaire survey to score each evaluation index, and uses the analytic hierarchy process (AHP) to calculate the weight of the index. Finally, the paper takes the public sports service of the elderly in a city as an example to verify. The results show that the level of sports public service for the elderly in this city is only 77,928. Especially the two aspects of allocation of sports venues and the use of funds are the most unsatisfactory ones. It can be targeted to improve these two aspects, so as to improve the level of public sports services for the elderly. It is hoped that, through this study, we can provide some reference for improving the level of sports public service for the elderly from the perspective of healthy aging.
RESUMO Com a melhoria gradual da qualidade de vida das pessoas, a expectativa média de vida do nosso país foi ampliada. Estima-se que o número total de pessoas idosas na China excederá 250 milhões até o final de 2020. Por isso, promover um envelhecimento saudável é uma medida necessária para lidar com a futura população idosa na China, e o exercício físico é um método importante para manter a saúde física e mental dos idosos. A fim de promover o desenvolvimento de um envelhecimento saudável na China, este estudo centrou-se no nível atual de serviços desportivos públicos para os idosos. Este trabalho utiliza o método de consulta de especialistas para testar a racionalidade do índice de avaliação, e utiliza o método de levantamento por questionário para marcar cada índice de avaliação, e utiliza o processo hierárquico analítico (AHP) para calcular o peso do índice. Finalmente, a pesquisa toma como exemplo o serviço público de desportos dos idosos numa cidade. Os resultados mostram que o nível de serviço público desportivo para os idosos nesta cidade é apenas 77.928. Em especial, os aspectos da atribuição de espaços desportivos e a utilização de recursos financeiros são os mais insatisfatórios. Pode visar-se melhorar esses dois aspectos, de modo a melhorar o nível dos serviços desportivos públicos para os idosos. Espera-se que, através deste estudo, possamos oferecer uma referência para melhorar o nível de serviço público desportivo para os idosos sob a perspectiva do envelhecimento saudável.
RESUMEN Con la mejora paulatina de la calidad de vida de las personas se ha ampliado la esperanza de vida media de nuestro país. Se estima que el número total de personas añosas en China superará los 250 millones a finales de 2020. Por lo tanto, promover un envejecimiento saludable es una medida necesaria para hacer frente al aumento de la edad de la sociedad en China. El ejercicio físico es un método importante para mantener la salud física y mental de las personas mayores. Con el fin de promover el desarrollo del envejecimiento saludable en China, este estudio se centró en el nivel actual de los servicios deportivos públicos para las personas añosas. Este estudio utiliza la consulta de expertos para probar la racionalidad del índice de evaluación, la encuesta de cuestionario para calificar cada índice de evaluación, y el proceso de jerarquía analítica (PJA) para calcular el peso del índice. Finalmente, el trabajo toma como ejemplo a ser verificado, el servicio público deportivo de la tercera edad en una ciudad determinada. Los resultados muestran que el nivel de servicio público deportivo para personas añosas en esa ciudad es de solo 77.928. Especialmente los aspectos de la asignación de instalaciones deportivas y del uso de fondos son los más insatisfactorios. Se debe apuntar a mejorar estos dos aspectos, a fin de conseguir un mejor nivel de servicios deportivos públicos para las personas añosas. Esperamos que, a través de este estudio, podamos proporcionar una referencia para mejorar el nivel de servicio público deportivo para las personas añosas desde la perspectiva del envejecimiento saludable.
Subject(s)
Humans , Aged , Healthy Aging , Public Health Services , Sports , ChinaABSTRACT
For the disadvantages of both the slow reaction kinetics and the poor conductivity for Nb2O5 electrode materials as sodium-ion capacitors (SICs), Nb2O5 NRs/NMMCNF film electrode with good flexibility and high electrochemical property has been fabricated by electrospinning PAN/PMMA/H2Nb2O6·H2O homogeneous viscous suspension and followed by an annealing treatment, in which the precursor H2Nb2O6·H2O nanorods are obtained by grinding H2Nb2O6·H2O nanowires, and Nb2O5 nanorods are uniformly embedded in nitrogen doped microporous multichannel carbon nanofiber. Benefiting from the multichannel network structure, Nb2O5 NRs/NMMCNF film electrode delivers the fast kinetics of Na+-storage and the superior Na-ion storage performance, it delivers outstanding rate capability (101 mAh g-1 at 4 A g-1) and ultralong lifespan (91% capacity retention after 10,000 cycles at 2 A g-1). A Nb2O5 NRs/NMMCNF//AC SIC based on the Nb2O5 NRs@NMMCNF fiber film anode and the AC cathode is assembled. The energy density of the as-assembled device is as high as 91 Wh kg-1 and its maximum power density is 7499 W kg-1. This work offers a new structure design strategy toward intercalation-type metal oxide electrodes for application in SICs.
ABSTRACT
BACKGROUND: Pyruvic acid (PA), a vital α-oxocarboxylic acid, plays an important role in energy and carbon metabolism. The oleaginous yeast Yarrowia lipolytica (Y. lipolytica) has considerable potential for the production of PA. An increased NaCl concentration reportedly increases the biomass and PA yield of Y. lipolytica. RESULTS: To increase the yield of PA, the NaCl-tolerant Y. lipolytica A4 mutant was produced using the atmospheric and room temperature plasma method of mutation. The A4 mutant showed growth on medium containing 160 g/L NaCl. The PA yield of the A4 mutant reached 97.2 g/L at 120 h (0.795 g/g glycerol) in a 20-L fermenter with glycerol as the sole carbon source, which was 28.9% higher than that of the parental strain. CONCLUSION: The PA yield from Y. lipolytica can be improved by increasing its NaCl tolerance.
Subject(s)
Pyruvic Acid/metabolism , Yarrowia/genetics , Yarrowia/metabolism , Osmotic Pressure , Yeasts , Carbon/metabolism , Sodium Chloride , Bioreactors , Salt Tolerance/genetics , Fermentation , Glycerol/metabolism , MutationABSTRACT
Bacillus sp. strain QHF158, a Gram-positive, spore-forming and parasporal crystal-secreting bacterium, was isolated from soil of Limushan National Forest Park in China. Here we present the significant feature of parasporal inclusions of this organism, together with the draft genome sequence and annotation. Phylogenetic analysis suggested that strain QHF158 is possibly a novel species, most closely related to Bacillus mycoides. Genome annotation results revealed that strain QHF158 did not contain any typical Cry or Cyt toxin coding gene. Furthermore, the mass spectrometry analyses demonstrated that the parasporal crystalline inclusions were encoded by the orf_05273 gene, with 95% similarity to the S-layer protein (SLP) EA1 of B. mycoides, which indicated that the parasporal crystal from Bacillus sp. strain QHF158 was mainly formed by SLP, instead of the typical Cry or Cyt toxin proteins.
Subject(s)
Bacillus/genetics , Genome, Bacterial , Inclusion Bodies/metabolism , Membrane Glycoproteins/metabolism , Bacillus/classification , Bacillus/isolation & purification , Bacillus/metabolism , Inclusion Bodies/genetics , Membrane Glycoproteins/genetics , Phylogeny , Soil MicrobiologyABSTRACT
The Mexican American population is among the fastest growing aging population and has a younger onset of cognitive decline. This group is also heavily burdened with metabolic conditions such as hypertension, diabetes, and obesity. Unfortunately, limited research has been conducted in this group. Understanding methylation alterations, which are influenced by both genetic and lifestyle factors, is key to identifying and addressing the root cause for mild cognitive impairment, a clinical precursor for dementia. We conducted an epigenome-wide association study on a community-based Mexican American population using the Illumina EPIC array. Following rigorous quality control measures, we identified 10 CpG sites to be differentially methylated between normal controls and individuals with mild cognitive impairment annotated to PKIB, KLHL29, SEPT9, OR2C3, CPLX3, BCL2L2-PABPN1, and CCNY. We found four regions to be differentially methylated in TMEM232, SLC17A8, ALOX12, and SEPT8. Functional gene-set analysis identified four gene-sets, RIN3, SPEG, CTSG, and UBE2L3, as significant. The gene ontology and pathway analyses point to neuronal cell death, metabolic dysfunction, and inflammatory processes. We found 1,450 processes to be enriched using empirical Bayes gene-set enrichment. In conclusion, the functional overlap of differentially methylated genes associated with cognitive impairment in Mexican Americans implies cross-talk between metabolically-instigated systemic inflammation and disruption of synaptic vesicular transport.
Subject(s)
Alzheimer Disease/genetics , Cognitive Dysfunction/genetics , DNA Methylation/physiology , Metabolic Diseases/genetics , Mexican Americans/genetics , Synaptic Transmission/physiology , Aged , Alzheimer Disease/blood , Alzheimer Disease/epidemiology , Cognitive Dysfunction/blood , Cognitive Dysfunction/epidemiology , Cohort Studies , Female , Genome-Wide Association Study , Humans , Male , Metabolic Diseases/blood , Metabolic Diseases/epidemiology , Middle Aged , Morbidity , Phenotype , Prodromal SymptomsABSTRACT
Mitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phenomena in Mexican Americans is of particular importance due to the disproportionate prevalence of both T2D and AD in this population. Here, we assessed the potential role of mitochondria in T2D and cognitive impairment (CI) in a Mexican American cohort by analyzing blood-based indices of mitochondrial DNA copy number (mtDNACN) and cell-free mitochondrial DNA (CFmtDNA). These mitochondrial metrics were also analyzed for correlation with relevant neuropsychological variables and physiological data collected as indicators of disease and/or disease progression. We found mtDNACN to be significantly decreased in individuals with CI, while CFmtDNA was significantly elevated in T2D; further, CFmtDNA elevation was significantly exacerbated in individuals with both diseases. MtDNACN was found to negatively correlate with age and fatty acid binding protein concentration, while positively correlating with CFmtDNA as well as CERAD total recall score. Candidate gene SNP-set analysis was performed on genes previously implicated in maintenance and control of mitochondrial dynamics to determine if nuclear variants may account for variability in mtDNACN. The results point to a single significant locus, in the LRRK2/MUC19 region, encoding leucine rich repeat kinase 2 and mucin 19. This locus has been previously implicated in Parkinson's disease, among others; rs7302859 was the driver SNP. These combined findings further indicate that mitochondrial dysfunction (as assessed by proxy via mtDNACN) is intimately linked to both T2D and CI phenotypes as well as aging.
Subject(s)
Cell-Free Nucleic Acids , Cognitive Dysfunction , DNA, Mitochondrial , Diabetes Mellitus, Type 2 , Mexican Americans , Aged , Alzheimer Disease/blood , Alzheimer Disease/ethnology , Alzheimer Disease/genetics , Cell-Free Nucleic Acids/blood , Cell-Free Nucleic Acids/genetics , Cognitive Dysfunction/blood , Cognitive Dysfunction/ethnology , Cognitive Dysfunction/genetics , DNA, Mitochondrial/blood , DNA, Mitochondrial/genetics , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/genetics , Female , Genetic Loci , Humans , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Male , Middle Aged , Mucins/genetics , Polymorphism, Single NucleotideABSTRACT
OBJECTIVES: To compare the results respectively obtained from the utilization of 60% barium sulfate suspension and Iohexol as contrast agents for videofluoroscopic swallowing studies and the relationship between the clinical application of the two kinds of contrast agents and the incidence of pneumonia. METHODS: Sixty cases of stroke patients with dysphagia were selected in rehabilitation department of our hospital, and the gender, age, position of the disease, and stroke nature between groups had no significant difference. Among which, 30 patients who were administered 350 mgI/ml Iohexol, and the other 30 patients with 60% barium sulfate suspension as contrast agent. We performed videofluoroscopic swallowing studies with barium 60% versus Iohexol within 1 week after admission and 2 weeks after admission. RESULTS: After 2 weeks in hospital, the aspiration pneumonia incidence of two groups was statistically significant (p<0.05), the pneumonia incidence of Iohexol group was lower than barium sulfate group which might have a impossble relevance with barium aspiration. CONCLUSIONS: During the videofluoroscopic swallowing study of dysphagia after stroke, barium sulfate can enhance the pneumonia incidence, and Iohexol can be widely applied in videofluoroscopic swallowing study.
Subject(s)
Barium Sulfate/adverse effects , Contrast Media/adverse effects , Deglutition Disorders/diagnostic imaging , Fluoroscopy/methods , Pneumonia, Aspiration/chemically induced , Adult , Aged , Barium Sulfate/administration & dosage , Contrast Media/administration & dosage , Deglutition/drug effects , Deglutition Disorders/complications , Female , Humans , Iohexol/administration & dosage , Iohexol/adverse effects , Male , Middle Aged , Pneumonia, Aspiration/diagnosis , Stroke Rehabilitation/methods , Video Recording/methodsABSTRACT
OBJECTIVES: To compare the results respectively obtained from the utilization of 60% barium sulfate suspension and Iohexol as contrast agents for videofluoroscopic swallowing studies and the relationship between the clinical application of the two kinds of contrast agents and the incidence of pneumonia. METHODS: Sixty cases of stroke patients with dysphagia were selected in rehabilitation department of our hospital, and the gender, age, position of the disease, and stroke nature between groups had no significant difference. Among which, 30 patients who were administered 350 mgI/ml Iohexol, and the other 30 patients with 60% barium sulfate suspension as contrast agent. We performed videofluoroscopic swallowing studies with barium 60% versus Iohexol within 1 week after admission and 2 weeks after admission. RESULTS: After 2 weeks in hospital, the aspiration pneumonia incidence of two groups was statistically significant (p<0.05), the pneumonia incidence of Iohexol group was lower than barium sulfate group which might have a impossble relevance with barium aspiration. CONCLUSIONS: During the videofluoroscopic swallowing study of dysphagia after stroke, barium sulfate can enhance the pneumonia incidence, and Iohexol can be widely applied in videofluoroscopic swallowing study.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Pneumonia, Aspiration/chemically induced , Barium Sulfate/adverse effects , Fluoroscopy/methods , Deglutition Disorders/diagnostic imaging , Contrast Media/adverse effects , Pneumonia, Aspiration/diagnosis , Barium Sulfate/administration & dosage , Video Recording/methods , Iohexol/administration & dosage , Iohexol/adverse effects , Deglutition Disorders/complications , Contrast Media/administration & dosage , Deglutition/drug effects , Stroke Rehabilitation/methodsABSTRACT
BACKGROUND: Regional differences in risk of diabetes mellitus and cardiovascular outcomes in people with impaired glucose tolerance are poorly characterized. Our objective was to evaluate regional variation in risk of new-onset diabetes mellitus, cardiovascular outcomes, and treatment effects in participants from the NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) trial. METHODS AND RESULTS: NAVIGATOR randomized people with impaired glucose tolerance and cardiovascular risk factors or with established cardiovascular disease to valsartan (or placebo) and to nateglinide (or placebo) with a median 5-year follow-up. Data from the 9306 participants were categorized by 5 regions: Asia (n=552); Europe (n=4909); Latin America (n=1406); North America (n=2146); and Australia, New Zealand, and South Africa (n=293). Analyzed outcomes included new-onset diabetes mellitus; cardiovascular death; a composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; and treatment effects of valsartan and nateglinide. Respective unadjusted 5-year risks for new-onset diabetes mellitus, cardiovascular death, and the composite cardiovascular outcome were 33%, 0.4%, and 4% for Asia; 34%, 2%, and 6% for Europe; 37%, 4%, and 8% for Latin America; 38%, 2%, and 6% for North America; and 32%, 4%, and 8% for Australia, New Zealand, and South Africa. After adjustment, compared with North America, European participants had a lower risk of new-onset diabetes mellitus (hazard ratio 0.86, 95% CI 0.78-0.94; P=0.001), whereas Latin American participants had a higher risk of cardiovascular death (hazard ratio 2.68, 95% CI 1.82-3.96; P<0.0001) and the composite cardiovascular outcome (hazard ratio 1.48, 95% CI 1.15-1.92; P=0.003). No differential interactions between treatment and geographic location were identified. CONCLUSIONS: Major regional differences regarding the risk of new-onset diabetes mellitus and cardiovascular outcomes in NAVIGATOR participants were identified. These differences should be taken into account when planning global trials. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00097786.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Cardiovascular Diseases/drug therapy , Cyclohexanes/therapeutic use , Glucose Intolerance/drug therapy , Hypoglycemic Agents/therapeutic use , Phenylalanine/analogs & derivatives , Valsartan/therapeutic use , Aged , Asia , Australia , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/epidemiology , Europe , Female , Humans , Incidence , Latin America , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/epidemiology , Nateglinide , New Zealand , North America , Outcome Assessment, Health Care , Phenylalanine/therapeutic use , Proportional Hazards Models , Randomized Controlled Trials as Topic , Risk Factors , South Africa , Stroke/epidemiologyABSTRACT
Allele frequencies for 15 autosomal STR loci (N = 290) and haplotype data for 17 Y-STR loci (N = 157) were determined for an admixed population from Belize. There were no detectable departures from Hardy-Weinberg equilibrium expectations at any autosomal STR loci except for the D8S1179 locus (p = 0.002). The combined power of discrimination (PD) and combined power of exclusion (PE) were greater than 0.99999999 and 0.99999951, respectively. In addition, a total of 144 distinct Y-STR haplotypes were observed with 133 Y-STR haplotypes observed only once. The most common Y-STR haplotype was observed three times for two separate haplotypes. The various analyses of these forensically relevant STR loci showed that these markers are informative in the Belize population for forensic and parentage testing applications.
Subject(s)
Chromosomes, Human, Y , DNA Fingerprinting , Gene Frequency , Genetics, Population , Microsatellite Repeats , Belize , Female , Haplotypes , Humans , Male , Polymerase Chain ReactionABSTRACT
BACKGROUND: Contemporary studies suggest an association between venous thromboembolism and a higher incidence of major cardiovascular events, mostly attributed to arterial atherothrombosis. Using data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, we assessed the association of venous thromboembolism with major cardiovascular events. METHODS: In NAVIGATOR, patients with impaired glucose tolerance were randomly allocated to receive valsartan or placebo and nateglinide or placebo in addition to lifestyle modification. Baseline characteristics and prior history of venous thromboembolism were assessed. After adjusting for important baseline covariates, Cox proportional hazards regression models were used to assess the association between venous thromboembolism and major cardiovascular outcomes. RESULTS: Of the 9306 patients enrolled, 129 (1.4%) had a history of venous thromboembolism. Patients with venous thromboembolism were older, more frequently white and female, and had a higher body mass index. Patients with venous thromboembolism had higher 5-year event rates for the composite of death, myocardial infarction, and stroke, as compared with patients without venous thromboembolism (10.7% vs 5.9%; P < .001; adjusted hazard ratio 2.12; 95% confidence interval, 1.36-3.31; P = .001). CONCLUSION: In patients with impaired glucose tolerance at high risk for cardiovascular events, the prevalence of venous thromboembolism was rare but associated with worse long-term cardiovascular outcomes, including arterial events. Venous thromboembolism is a marker of risk, and attention should be paid to this high-risk group of patients.