| 1. |
- Abbafati, Cristiana, et al.
(författare)
-
- 2020
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Teufel, Felix, et al.
(författare)
-
Analysis of Attained Height and Diabetes Among 554,122 Adults Across 25 Low- and Middle-Income Countries
- 2020
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:10, s. 2403-2410
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The prevalence of type 2 diabetes is rising rapidly in low-income and middle-income countries (LMICs), but the factors driving this rapid increase are not well understood. Adult height, in particular shorter height, has been suggested to contribute to the pathophysiology and epidemiology of diabetes and may inform how adverse environmental conditions in early life affect diabetes risk. We therefore systematically analyzed the association of adult height and diabetes across LMICs, where such conditions are prominent.RESEARCH DESIGN AND METHODS: We pooled individual-level data from nationally representative surveys in LMICs that included anthropometric measurements and diabetes biomarkers. We calculated odds ratios (ORs) for the relationship between attained adult height and diabetes using multilevel mixed-effects logistic regression models. We estimated ORs for the pooled sample, major world regions, and individual countries, in addition to stratifying all analyses by sex. We examined heterogeneity by individual-level characteristics.RESULTS: Our sample included 554,122 individuals across 25 population-based surveys. Average height was 161.7 cm (95% CI 161.2-162.3), and the crude prevalence of diabetes was 7.5% (95% CI 6.9-8.2). We found no relationship between adult height and diabetes across LMICs globally or in most world regions. When stratifying our sample by country and sex, we found an inverse association between adult height and diabetes in 5% of analyses (2 out of 50). Results were robust to alternative model specifications.CONCLUSIONS: Adult height is not associated with diabetes across LMICs. Environmental factors in early life reflected in attained adult height likely differ from those predisposing individuals for diabetes.
|
|
| 3. |
- Coombes, D., et al.
(författare)
-
The basis for non-canonical ROK family function in the N-acetylmannosamine kinase from the pathogen Staphylococcus aureus
- 2020
-
Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 295:10, s. 3301-3315
-
Tidskriftsartikel (refereegranskat)abstract
- In environments where glucose is limited, some pathogenic bacteria metabolize host-derived sialic acid as a nutrient source. N-Acetylmannosamine kinase (NanK) is the second enzyme of the bacterial sialic acid import and degradation pathway and adds phosphate to N-acetylmannosamine using ATP to prime the molecule for future pathway reactions. Sequence alignments reveal that Gram-positive NanK enzymes belong to the Repressor, ORF, Kinase (ROK) family, but many lack the canonical Zn-binding motif expected for this function, and the sugar-binding EXGH motif is altered to EXGY. As a result, it is unclear how they perform this important reaction. Here, we study the Staphylococcus aureus NanK (SaNanK), which is the first characterization of a Gram-positive NanK. We report the kinetic activity of SaNanK along with the ligand?free, N-acetylmannosamine?bound and substrate analog GlcNAc?bound crystal structures (2.33, 2.20, and 2.20 ? resolution, respectively). These demonstrate, in combination with small-angle X-ray scattering, that SaNanK is a dimer that adopts a closed conformation upon substrate binding. Analysis of the EXGY motif reveals that the tyrosine binds to the N-acetyl group to select for the ?boat? conformation of N-acetylmannosamine. Moreover, SaNanK has a stacked arginine pair coordinated by negative residues critical for thermal stability and catalysis. These combined elements serve to constrain the active site and orient the substrate in lieu of Zn binding, representing a significant departure from canonical NanK binding. This characterization provides insight into differences in the ROK family and highlights a novel area for antimicrobial discovery to fight Gram-positive and S. aureus infections.
|
|
| 4. |
- Sepanlou, Sadaf G., et al.
(författare)
-
The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
- 2020
-
Ingår i: The Lancet Gastroenterology & Hepatology. - 2468-1253. ; 5:3, s. 245-266
-
Tidskriftsartikel (refereegranskat)abstract
- Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH.
|
|
| 5. |
- Karlsson, Omar, et al.
(författare)
-
Changing speed of reduction in under-5 mortality rates over the 20th century
- 2020
-
Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 1470-2738 .- 0143-005X. ; 75:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Declines from high levels of under-5 mortality rate (U5MR) first occurred in Western Europe. Knowledge and technologies gained from early mortality reductions could accelerate the U5MR decline for countries that followed. We explored whether average annual reduction (AAR) in U5MR increased between countries over time in the 20th century.Methods We used U5MR time series from the Human Mortality Database and United Nations for 110 countries experiencing a decline from 100 to 50 under-5 deaths per 1000 live births during the 20th century.Results Between 1907 and 1938, the AAR was 2.61 (95% CI 2.09, 3.13) deaths per 1000 live births per year on average and increased by 0.06 (95% CI 0.02, 0.10) deaths for each year that passed before the decline started. Countries going through the decline in 1938–1968 and 1968–1999 showed an AAR of 3.96 and 3.67 (95% CI 3.37, 4.54 and 3.26, 4.07), respectively, with no increase in AAR.Conclusions Acceleration in U5MR reduction was apparent in today’s high-income countries, indicating that greater similarities and capacity may have facilitated the adaptation of mortality reducing knowledge and technologies. Greater emphasis on simple and individual-level interventions or more difficult circumstances may also explain the lack of acceleration in mortality reduction after 1950.
|
|
| 6. |
|
|
| 7. |
- Subramanian, M. L., et al.
(författare)
-
Neurofilament light chain in the vitreous humor of the eye
- 2020
-
Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases. Methods This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5-1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (A beta), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins,APOEgenotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases. Results NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of A beta(40)(p = 7.7 x 10(-5)), A beta(42)(p = 2.8 x 10(-4)), and t-tau (p = 5.5 x 10(-7)), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15,p = 5.3 x 10(-4)), IL-16 (p = 2.2 x 10(-4)), monocyte chemoattractant protein-1 (MCP1,p = 4.1 x 10(-4)), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1,p = 2.9 x 10(-6)), Vegf-C (p = 8.6 x 10(-6)), vascular cell adhesion molecule-1 (VCAM-1,p = 5.0 x 10(-4)), Tie-2 (p = 6.3 x 10(-4)), and intracellular adhesion molecular-1 (ICAM-1,p = 1.6 x 10(-4)). Conclusion NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients' clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.
|
|
| 8. |
- Subramanian, S. V., et al.
(författare)
-
Geo-mapping of COVID-19 Risk Correlates Across Districts and Parliamentary Constituencies in India
- 2020
-
Ingår i: Harvard Data Science Review. - 2644-2353.
-
Tidskriftsartikel (refereegranskat)abstract
- In the current stage of the COVID-19 pandemic, as countries open up after an extended period of lockdown, it is important to assure the population that their health is not being sacrificed. In this article, we develop a geomapping approach to identify high-risk areas by considering four nonclinical risk correlates for COVID-19. These are population density, percentage of the population that is exposed to crowding in a household, percentage of the population without access to handwashing facilities, and percentage of the population over 65 years of age. We provide an empirical proof-of-concept demonstration for this approach for India at two critical geographic units: districts and parliamentary constituencies, collectively responsible for policy administration and governance. Our findings suggest that the geographies of the four nonclinical risk correlates are largely independent of one another (i.e., at most, there is a small correlation between measures). We avoid applying differential weights to the four measures or combining these measures into a single index, as there is an intrinsic rationale for viewing them separately since they represent mostly independent dimensions of risks that require different responses. Our primary objective was to leverage currently available data to provide decision makers detailed information and geovisualization, identifying areas with potentially differential susceptibilities to COVID-19. The information provided here can be used as a means for further ground verification and, when appropriate, for impact planning and intervention, as well as providing a rationale for eventual efficacy assessment of different nonpharmaceutical interventions. While this exercise is primarily descriptive at this stage, the estimates generated are new, rigorous, and have high relevance for timely policy discussions. We use data from the Demographic and Health Surveys, which have extensive geographic coverage and high level of standardizations, making our highly accessible approach easy to extend to other low- and middle-income countries. We share this conceptualization of geomapping, and all the data and codes used for this exercise, to encourage wider applications and advancements.
|
|
