| 1. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 2. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 3. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 4. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 5. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 6. |
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| 7. |
- Devaprasad, M., et al.
(författare)
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Characterization of paddy-residue burning derived carbonaceous aerosols using dual carbon isotopes
- 2023
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 864
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Tidskriftsartikel (refereegranskat)abstract
- A large scale paddy-residue burning (PRB) happens every year in the northwest Indo-Gangetic Plain (IGP) during the post-monsoon season, and winds transport pollutants from the source region up to the northern Indian Ocean affecting air quality of the IGP and marine region. In this study, day-night pairs of fine aerosol samples (n = 69) were collected during October–November over Patiala (30.2°N, 76.3°E, 250 m amsl), a site located in the source region of PRB. Carbonaceous aerosols (CA) were characterised using chemical species and dual carbon isotopes (13C and 14C) to estimate bio vs non-bio contributions and understand their characteristics. Percentage of bio fraction (fbio, estimated using 14C) in CA varied from 74 % to 87 % (avg: 80 ± 3) during days and 71 % to 96 % (avg: 85 ± 7 %) during nights. Further, the fbio was found to be better correlated with aerosol mass spectrometer derived f60 compare to levoglucosan (LG) or nssK+, suggesting f60 a useful proxy for PRB. The δ13C varied from −27.7 ‰ to −26.0 ‰ (avg: −27.0 ± 0.4 ‰) and − 28.7 ‰ to −26.4 ‰ (avg: −27.5 ± 0.7 ‰) during day and night, respectively. Measured δ13C of the samples was found to be more enriched than expected by 0.3 to 2.0 ‰, indicating the presence of aged CA also in Patiala even during PRB period. From fbio versus δ13C correlation, and from Miller-Trans plot, δ13C of PRB is found to be −28.9 ± 1.1 ‰, which also infers that Miller-Trans plot can be used to understand source isotopic signature in the absence of radiocarbon measurements in aerosols. Further, the characteristics ratios of organic carbon (OC) to elemental carbon (EC) (11.9 ± 4.1), LG to potassium (K+) (0.84 ± 0.15), OC/LG (19.7 ± 2.0) and K+/EC (0.75 ± 0.27) were calculated by considering samples with fbio higher than 0.90, which can be used for source apportionment studies. Such studies are crucial in assessing the effects of PRB on regional air quality and climate.
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| 8. |
- Raj, Satish R, et al.
(författare)
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Postural orthostatic tachycardia syndrome (POTS) : Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2
- 2021
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Ingår i: Autonomic Neuroscience: Basic & Clinical. - : Elsevier BV. - 1872-7484. ; 235
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Tidskriftsartikel (refereegranskat)abstract
- The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.
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| 9. |
- Vernino, Steven, et al.
(författare)
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Postural orthostatic tachycardia syndrome (POTS) : State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1
- 2021
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Ingår i: Autonomic Neuroscience: Basic and Clinical. - : Elsevier BV. - 1566-0702. ; 235
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Tidskriftsartikel (refereegranskat)abstract
- Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.
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| 10. |
- Arunachalam, Natarajan, et al.
(författare)
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Community-based control of Aedes aegypti by adoption of eco-health methods in Chennai City, India.
- 2012
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Ingår i: Pathogens and global health. - 2047-7732. ; 106:8, s. 488-96
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Tidskriftsartikel (refereegranskat)abstract
- Dengue is highly endemic in Chennai city, South India, in spite of continuous vector control efforts. This intervention study was aimed at establishing the efficacy as well as the favouring and limiting factors relating to a community-based environmental intervention package to control the dengue vector Aedes aegypti.
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| 11. |
- Brignole, Michele, et al.
(författare)
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Low-blood pressure phenotype underpins the tendency to reflex syncope
- 2021
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Ingår i: Journal of Hypertension. - 1473-5598. ; 39:7, s. 1319-1325
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We hypothesized that cardiovascular physiology differs in reflex syncope patients compared with the general population, predisposing such individuals to vasovagal reflex.METHODS: In this multicohort cross-sectional study, we compared aggregate data of resting SBP, DBP, pulse pressure (PP) and heart rate (HR), collected from six community-based cohort studies (64 968 observations) with those from six databases of reflex syncope patients (6516 observations), subdivided by age decades and sex.RESULTS: Overall, in male individuals with reflex syncope, SBP (-3.4 mmHg) and PP (-9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages above 60 years. In female individuals, PP (-6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with male individuals, SBP in female individuals exhibited slower increase until age 40 years, and then demonstrated steeper increase that continued throughout remaining life.CONCLUSION: The patients prone to reflex syncope demonstrate a different resting cardiovascular haemodynamic profile as compared with a general population, characterized by lower SBP and PP, reflecting reduced venous return and lower stroke volume, and a higher HR and DBP, suggesting the activation of compensatory mechanisms. Our data contribute to a better understanding why some individuals with similar demographic characteristics develop reflex syncope and others do not.VIDEO ABSTRACT: http://links.lww.com/HJH/B580.
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| 12. |
- Chauhan, Hetal R., et al.
(författare)
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Role of micro- and nano-CeO 2 reinforcements on characteristics and tribological performance of HVOF sprayed Cr3C2-NiCr coatings
- 2023
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Ingår i: Surface and Coatings Technology. - 0257-8972 .- 1879-3347. ; 467
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigates the role of micro- and nano-CeO2 reinforcements on microstructural, mechanical and tribological properties of Cr3C2-NiCr coatings deposited using high-velocity-oxy-fuel (HVOF) spray process. A novel blending method involving ultrasonication, magnetic stirring and 3D-tumbler mixing was used to prepare the micro- and nano-CeO2 reinforced Cr3C2-NiCr feedstock powders. Unreinforced Cr3C2-NiCr coatings were also prepared for comparison purposes. X-ray diffraction, FE-SEM, EDS mapping, optical microscopy and optical profilometry were used to characterize the coatings. Tribological studies were performed on the coatings using modular ball-on-disc tribometer. The results showed that nano-CeO2 reinforced coatings yielded considerable reduction in porosity, surface roughness and CoF values while significantly enhancing the hardness and fracture toughness in comparison to the micro-CeO2 reinforced and unreinforced Cr3C2-NiCr coatings. The addition of nanoCeO2 to the coatings contributed to the microstructure refinement and to the formation of stable tribo-oxide layer, resulting in a lower specific wear rate under identical test conditions. Performance of micro-CeO2 reinforced coatings was intermediate to that of nano-CeO2 reinforced and unreinforced Cr3C2-NiCr coatings.
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| 13. |
- Fedorowski, Artur, et al.
(författare)
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Cardiovascular autonomic dysfunction in post-COVID-19 syndrome : a major health-care burden
- 2024
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Ingår i: Nature Reviews Cardiology. - 1759-5002 .- 1759-5010. ; 21:6, s. 379-395
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Forskningsöversikt (refereegranskat)abstract
- Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.
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| 14. |
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| 15. |
- Govind, Satish C., et al.
(författare)
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Impaired Myocardial Functional Reserve in Hypertension and Diabetes Mellitus Without Coronary Artery Disease: Searching for the Possible Link With Congestive Heart Failure in the Myocardial Doppler in Diabetes (MYDID) Study II
- 2006
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 19:8, s. 851-857
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although the impact of type 2 diabetes mellitus (DM) and hypertension (HTN) on myocardial function has recently been studied using tissue Doppler echocardiography (TDE), the independent role of both conditions, and the influence of other risk factors on myocardial function has not been completely defined, particularly in absence of coronary artery disease (CAD). The aim of this study was to assess the myocardial functional reserve in patients with DM or HTN with apparently normal left ventricular (LV) systolic function. Methods: Standard and dobutamine stress echocardiography using TDE was performed in 128 subjects: 59 had DM, 20 had HTN, 27 had both DM and HTN (HTN + DM), and 22 subjects were controls (C). Subjects with known CAD and depressed LV function were excluded. In addition, standard two-dimensional and Doppler measurements, LV regional peak systolic (PSV), early (E') and late (A') diastolic velocities, strain (S%) and strain rate (SR), were assessed at rest and peak stress. Results: The LV mass did not differ, although relative wall thickness was significantly higher in subjects with HTN + DM and HTN. The PSV did not differ at rest but was lowest in subjects with HTN + DM at peak stress. The E' wave velocity was significantly lower in subjects with HTN + DM both at rest and during peak stress, as were S% and SR. Conclusions: The addition of DM to HTN has a negative effect on LV systolic and diastolic functions. A depressed myocardial functional reserve might be postulated as one of the pathophysiologic mechanisms for the excessive occurrence of congestive heart failure in patients with DM or HTN.
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| 16. |
- Govind, Satish C., et al.
(författare)
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Isolated Type 2 Diabetes mellitus Causes Myocardial Dysfunction That Becomes Worse in the Presence of Cardiovascular Diseases : Results of the Myocardial Doppler in Diabetes (MYDID): Study 1
- 2005
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Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 103:4, s. 189-195
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Patients with type 2 diabetes mellitus (DM) often suffer disproportionately and have a worse outcome when burdened with cardiovascular complications compared with those without DM. A specific heart muscle disease reportedly caused by DM per se may explain this. We sought to investigate whether an echo Doppler diagnosis of such a myocardial disease is clinically relevant in DM with or without coexistent coronary artery disease (CAD) and/or hypertension ( HTN). Subjects and Methods: Two hundred subjects (127 males, 73 females, 56 +/- 10 years) including controls (n=23), patients with HTN (n=20), CAD (n=35), uncomplicated DM (n=59), DM+HTN (n=27), DM+ CAD (n=16) and DM+CAD+HTN (n=20) underwent tissue Doppler-enhanced dobutamine stress echocardiography. Myocardial function was assessed by measuring left ventricular myocardial peak systolic velocity (PSV) and early diastolic velocity at rest and during peak stress, besides measurements of standard Doppler variables. Results: Average left ventricular PSV at rest was significantly lower in CAD (4.7 +/- 1.5) compared with controls (5.7 center dot +/- 1.2) and in DM+CAD+HTN (4.6 +/- 1.4) compared with DM (5.6 +/- 1.3; all p < 0.05). During peak stress, lower PSV persisted in CAD (9.5 +/- 3.1) and DM+CAD+HTN (8.1 +/- 2.7), while appearing de novo in DM (11.3 +/- 2.6) and HTN (11.0 +/- 2.3) unlike in the controls (12.5 +/- 2.5; all p < 0.001). When pooled together, DM subjects with CAD and/or HTN or both had significantly lower PSV (9.1 +/- 2.7) than those without (10.0 +/- 2.8; p < 0.001). Early diastolic velocity response was equally lower in both groups compared with the controls. Conclusion: The results suggest that dobutamine stress unmasks myocardial functional disturbances caused by uncomplicated DM. The discrete disturbances become quantitatively more pronounced in the presence of coexistent cardiovascular diseases.
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| 17. |
- Govind, Satish C., et al.
(författare)
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Microalbuminuria and Left Ventricular Functions in Type 2 Diabetes : A Quantitative Assessment by Stress Echocardiography in the Myocardial Doppler in Diabetes (MYDID) Study III
- 2007
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Ingår i: International Journal of Cardiology. - : Informa UK Limited. - 0167-5273 .- 1874-1754. ; 41:6, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- Background. Left ventricular (LV) function might be altered in type 2 diabetes (DM) and microalbuminuria (MA) may accentuate the abnormalities. We sought to investigate whether additional LV dysfunction could be unmasked using tissue Doppler (TVE)-enhanced dobutamine stress echocardiography (TVE-DSE) in patients with DM+MA. Methods. Twenty seven DM subjects with MA, (DM+MA), 31 DM subjects without MA (DM-MA), and 13 Controls were evaluated using TVE-DSE. LV basal peak systolic (PSV), early (E') and late (A') diastolic velocities (cm/sec) at rest and peak stress were post-processed. LV filling pressure was assessed using E/E'ratio. Results. PSV and E'velocity at peak stress in the respective three groups were 13.7±1.0, 10.1±1.1, 10.0±1.2 for PSV; and 10.0±1.6, 5.0±1.4, 4.8±1.4 for E' (p < 0.001 for controls vs. both groups). E/E' at rest was 7.9±0.7 in the controls, 10.8±2.4 in DM-MA, and 11.0±2.2 in DM+MA (p < 0.01 Controls vs. both the DM groups). Conclusions. Patients with DM+MA do not have additional LV regional systolic and diastolic dysfunctions compared with DM-MA, as revealed by TVE-DSE, when controlled for glycemia levels, lipids, and treatment strategies.
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| 18. |
- Graham, Lesley A, et al.
(författare)
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Validation of Uromodulin as a Candidate Gene for Human Essential Hypertension
- 2014
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 63:3, s. 551-558
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Tidskriftsartikel (refereegranskat)abstract
- A recent genome-wide association study identified a locus on chromosome 16 in the promoter region of the uromodulin (UMOD) gene that is associated with hypertension. Here, we examined the hypertension signal with functional studies in Umod knockout (KO) mice. Systolic blood pressure was significantly lower in KO versus wild-type (WT) mice under basal conditions (KO: 116.6±0.3 mm Hg versus WT: 136.2±0.4 mm Hg; P<0.0001). Administration of 2% NaCl did not alter systolic blood pressure in KO mice, whereas it increased in WT mice by ≈33%, P<0.001. The average 24-hour urinary sodium excretion in the KO was greater than that of WT mice (P<0.001). Chronic renal function curves demonstrate a leftward shift in KO mice, suggesting that the relationship between UMOD and blood pressure is affected by sodium. Creatinine clearance was increased during salt loading with 2% NaCl in the KO mice, leading to augmented filtered Na(+) excretion and further Na(+) loss. The difference in sodium uptake that exists between WT and KO strains was explored at the molecular level. Urinary tumor necrosis factor-α levels were significantly higher in KO mice compared with WT mice (P<0.0001). Stimulation of primary thick ascending limb of the loop of Henle cells with exogenous tumor necrosis factor-α caused a reduction in NKCC2A expression (P<0.001) with a concurrent rise in the levels of UMOD mRNA (P<0.001). Collectively, we demonstrate that UMOD regulates sodium uptake in the thick ascending limb of the loop of Henle by modulating the effect of tumor necrosis factor-α on NKCC2A expression, making UMOD an important determinant of blood pressure control.
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| 19. |
- Hall, Juliette, et al.
(författare)
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Detection of G Protein-Coupled Receptor Autoantibodies in Postural Orthostatic Tachycardia Syndrome Using Standard Methodology
- 2022
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Ingår i: Circulation. - 1524-4539. ; 146:8, s. 613-622
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein-coupled receptors between patients with POTS and healthy controls.METHODS: Sera were collected from 116 patients with POTS (91% female; mean age, 29 years) and 81 healthy controls (84% female; mean age, 27 years) from Calgary, Canada, and Malmö, Sweden. Samples were evaluated for autoantibodies to 11 receptors (adrenergic, muscarinic, angiotensin II, and endothelin) using a commercially available enzyme-linked immunosorbent assay.RESULTS: Autoantibody concentrations against all of the receptors tested were not significantly different between controls and patients with POTS. The majority of patients with POTS (98.3%) and all controls (100%) had α1 adrenergic receptor autoantibody concentrations above the seropositive threshold provided by the manufacturer (7 units/mL). The proportion of patients with POTS versus healthy controls who fell above the diagnostic thresholds was not different for any tested autoantibodies. Receiver operating characteristic curves showed a poor ability to discriminate between patients with POTS and controls.CONCLUSION: Patients with POTS and healthy controls do not differ in their enzyme-linked immunosorbent assay-derived autoantibody concentrations to cardiovascular G protein-coupled receptors. These findings suggest that these tests are not useful for establishing the role of autoimmunity in POTS.
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| 20. |
- Mitra, Mainak, et al.
(författare)
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Nonheme Fe(IV) Oxo Complexes of Two New Pentadentate Ligands and Their Hydrogen-Atom and Oxygen-Atom Transfer Reactions
- 2015
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 1520-510X .- 0020-1669. ; 54:15, s. 7152-7164
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Tidskriftsartikel (refereegranskat)abstract
- Two new pentadentate {N5} donor ligands based on the N4Py (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) framework have been synthesized, viz. [N-(1-methyl-2-benzimidazolyl)methyl-N-(2-pyridyl)methyl-N-(bis-2-pyridyl methyl)amine] (L1) and [N-bis(1-methyl-2-benzimidazolyl)methyl-N-(bis-2-pyridylmethyl)amine] (L2), where one or two pyridyl arms of N4Py have been replaced by corresponding (N-methyl)benzimidazolyl-containing arms. The complexes [FeII(CH3CN)(L)]2+ (L = L1 (1); L2 (2)) were synthesized, and reaction of these ferrous complexes with iodosylbenzene led to the formation of the ferryl complexes [FeIV(O)(L)]2+ (L = L1 (3); L2 (4)), which were characterized by UV–vis spectroscopy, high resolution mass spectrometry, and Mössbauer spectroscopy. Complexes 3 and 4 are relatively stable with half-lives at room temperature of 40 h (L = L1) and 2.5 h (L = L2). The redox potentials of 1 and 2, as well as the visible spectra of 3 and 4, indicate that the ligand field weakens as ligand pyridyl substituents are progressively substituted by (N-methyl)benzimidazolyl moieties. The reactivities of 3 and 4 in hydrogen-atom transfer (HAT) and oxygen-atom transfer (OAT) reactions show that both complexes exhibit enhanced reactivities when compared to the analogous N4Py complex ([FeIV(O)(N4Py)]2+), and that the normalized HAT rates increase by approximately 1 order of magnitude for each replacement of a pyridyl moiety; i.e., [FeIV(O)(L2)]2+ exhibits the highest rates. The second-order HAT rate constants can be directly related to the substrate C–H bond dissociation energies. Computational modeling of the HAT reactions indicates that the reaction proceeds via a high spin transition state.
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| 21. |
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| 22. |
- Singh, Atinderpal, et al.
(författare)
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Wintertime oxidative potential of PM2.5 over a big urban city in the central Indo-Gangetic Plain
- 2023
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Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 905
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Tidskriftsartikel (refereegranskat)abstract
- Indo-Gangetic Plain (IGP) experiences a heavy load of particulate pollution impacting the 9 % of the global population living in this region. The present study examines the dithiothreitol (DTT) assay-based oxidative potential (OP) of PM2.5 and the major sources responsible for the observed OP over the central IGP (Kanpur) during winter. The volume normalized OP (OPV) of PM2.5 varied from 2.7 to 10 nmol DTT min(-1) m(-3) (5.5 +/- 1.5) and mass normalized OP (OPM) of PM2.5 varied from 19 to 58 pmol DTT min(-1) mu g(-1) (34 +/- 8.0), respectively. Major sources of PM2.5 were identified using the positive matrix factorization (PMF) and the contribution of these sources to observed OP was estimated through multivariate linear regression of OPv with PMF-resolved factors. Although the PM2.5 mass was dominated by secondary aerosols (SA, 28 %), followed by crustal dust (CD, 24 %), resuspended fine dust (RFD, 14 %), traffic emissions (TE, 8 %), industrial emissions (IE, 17 %), and trash burning (TB, 9 %), their proportionate contribution to OP (except SA) was different likely due to differences in redox properties of chemical species coming from these sources. The SA showed the highest contribution (23 %) to observed OP, followed by RFD (19 %), IE (8 %), TE & TB (5 %), CD (4 %), and others (36 %). Our results highlight the significance of determining the chemical composition of particulates along with their mass concentrations for a better understanding of the relationship between PM and health impacts. Such studies are still lacking in the literature, and these results have direct implications for making better mitigation strategies for healthier air quality.
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| 23. |
- Srivastava, R., et al.
(författare)
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Analysis of glutamine synthetase (glnA) gene from prokaryotic and eukaryotic organisms
- 2004
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Ingår i: Physiology and Molecular Biology of Plants. - 0971-5894. ; 10:2, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- Glutamine synthetase (GS) is a key enzyme involved in nitrogen metabolism that performs the essential biochemical function of ammonium assimilation and glutamine synthesis. The enzyme and its isoforms are present universally in all organisms and display diverse regulatory patterns. In this study, we have analyzed some sequences upstream and downstream the initiation codon of the structural gene of GS (glnA) to show that these sequences are involved in regulation and stable expression of the enzyme. GS is known to be regulated by adenylylation-deadenylylation cascade in some organisms. Analysis of the adenylylation site from several organisms revealed that the site could also be deciphered from those organisms where regulation of the enzyme is not known by adenylylation. The adenylylation site was mutated by the use of Swiss-PdbViewer and possible reasons were assigned to the functional and nonfunctional properties of this site in various organisms. This analysis has also helped in assigning functional relationships to some conserved sequences within and in the proximity of the glnA gene.
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| 24. |
- Srivastava, R., et al.
(författare)
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In silico analysis of thioredoxins and glutaredoxins
- 2005
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Ingår i: Journal of Plant Biochemistry and Biotechnology. - 0971-7811 .- 0974-1275. ; 14:2, s. 121-126
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Tidskriftsartikel (refereegranskat)abstract
- Thioredoxins (TRXs) and glutaredoxins (GRXs) are ubiquitous small redox proteins belonging to the thioredoxin (TRX) superfamily. They regulate several cellular functions via mediating a dithiol/disulphide exchange in target proteins. Thioredoxins have been classified into several subgroups based on their structural homologs. In an attempt to identify thioredoxin proteins which have not been characterized, an EST database survey of Lycopersicon esculentum, Glycine max, Helianthus annus, Secale cereale, Solanum tuberosum, Apis mellifera ligustica, Oncorhynchus mykiss, Salmo salar, and whole genome survey for Drosophila melanogaster, Rattus norvegicus and Caenorhabditis briggsae was performed. Several glutaredoxin and glutaredoxin-like proteins from Ricinus communis, Vercinia fordii, Lycopersicon esculentum, Tilia platyphyllos, Populus tremuloides, Triticum aestivum and Oryza sativa were also characterized. The deduced amino acid sequences were aligned and phylogenetic trees were constructed to determine the consensus sequences and for establishing interrelationships amongst the new and established thioredoxin and glutaredoxins. Based on the alignments, proteins were designated to their respective classes and subcellular localization predictions were used to predict their possible site of actions. In silico analysis has identified several new thioredoxins, glutaredoxins and related proteins and provided insight into their evolutionary relationships.
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| 25. |
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| 26. |
- Yu, Xichun, et al.
(författare)
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Angiotensin II type 1 receptor autoantibodies in postural tachycardia syndrome
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Background--Both the adrenergic and renin-angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1-adrenergic and β1/2-adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity. This study examines a possible pathophysiological role for AT1R autoantibodies in POTS. Methods and Results--Serum immunoglobulin G from 17 patients with POTS, 6 patients with recurrent vasovagal syncope, and 10 normal controls was analyzed for the ability to activate AT1R and alter AT1R ligand responsiveness in transfected cells in vitro. Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. AT1R activation by POTS immunoglobulin G was specifically blocked by the AT1R blocker losartan. Moreover, POTS immunoglobulin G significantly shifted the angiotensin II dosage response curve to the right, consistent with an inhibitory effect. All subjects with POTS were positive for one or both autoantibodies to the AT1R and α1-adrenergic receptor. Conclusions--Most patients with POTS harbor AT1R antibody activity. This supports the concept that AT1R autoantibodies and antiadrenergic autoantibodies, acting separately or together, may exert a significant impact on the cardiovascular pathophysiological characteristics in POTS.
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