| 1. |
- Pulit, S. L., et al.
(author)
-
Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
-
In: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
-
Journal article (peer-reviewed)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
|
|
| 2. |
|
|
| 3. |
- Marini, S., et al.
(author)
-
Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
- 2019
-
In: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
-
Journal article (peer-reviewed)abstract
- IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
|
|
| 4. |
- Shellock, R. J., et al.
(author)
-
Building leaders for the UN Ocean Science Decade : a guide to supporting early career women researchers within academic marine research institutions
- 2023
-
In: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 80:1, s. 56-75
-
Journal article (peer-reviewed)abstract
- Diverse and inclusive marine research is paramount to addressing ocean sustainability challenges in the 21st century, as envisioned by the UN Decade of Ocean Science for Sustainable Development. Despite increasing efforts to diversify ocean science, women continue to face barriers at various stages of their career, which inhibits their progression to leadership within academic institutions. In this perspective, we draw on the collective experiences of thirty-four global women leaders, bolstered by a narrative review, to identify practical strategies and actions that will help empower early career women researchers to become the leaders of tomorrow. We propose five strategies: (i) create a more inclusive culture, (ii) ensure early and equitable career development opportunities for women ECRs, (iii) ensure equitable access to funding for women ECRs, (iv) offer mentoring opportunities and, (v) create flexible, family-friendly environments. Transformational, meaningful, and lasting change will only be achieved through commitment and collaborative action across various scales and by multiple stakeholders.
|
|
| 5. |
- Anderson, Christopher D., et al.
(author)
-
Genetic variants in CETP increase risk of intracerebral hemorrhage
- 2016
-
In: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 80:5, s. 730-740
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10(-4) ) with no heterogeneity across studies (I(2) = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10(-6) ).INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.
|
|
| 6. |
- Gron, K. L., et al.
(author)
-
The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. : Results from 34 countries participating in the Quest-RA programme
- 2014
-
In: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 32:6, s. 869-877
-
Journal article (peer-reviewed)abstract
- Objective The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Methods Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10 worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score MAW) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. Results Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Conclusion Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.
|
|
| 7. |
- Hagag, Naglaa M., et al.
(author)
-
Isolation of a Novel Reassortant Highly Pathogenic Avian Influenza (H5N2) Virus in Egypt
- 2019
-
In: Viruses. - : MDPI. - 1999-4915. ; 11:6
-
Journal article (peer-reviewed)abstract
- Highly pathogenic avian influenza (HPAI) H5N1 and H5N8 have become endemic among domestic poultry in Egypt since 2006 and 2016, respectively. In parallel, the low pathogenic avian influenza H9N2 virus has been endemic since 2010. Despite the continuous circulation of these subtypes for several years, no natural reassortant has been detected so far among the domestic poultry population in Egypt. In this study, the HPAI (H5N2) virus was isolated from a commercial duck farm, giving evidence of the emergence of the first natural reassortment event in domestic poultry in Egypt. The virus was derived as a result of genetic reassortment between avian influenza viruses of H5N8 and H9N2 subtypes circulating in Egypt. The exchange of the neuraminidase segment and high number of acquired mutations might be associated with an alteration in the biological propensities of this virus.
|
|
| 8. |
- Krys, K, et al.
(author)
-
Happiness Maximization Is a WEIRD Way of Living
- 2024
-
In: Perspectives on psychological science : a journal of the Association for Psychological Science. - 1745-6924. ; , s. 17456916231208367-
-
Journal article (peer-reviewed)
|
|
| 9. |
- Alsoghier, H. M., et al.
(author)
-
NMR spectroscopic investigation of benzothiazolylacetonitrile azo dyes : CR7 substitution effect and semiempirical study
- 2021
-
In: RESULTS IN CHEMISTRY. - : Elsevier. - 2211-7156. ; 3
-
Journal article (peer-reviewed)abstract
- Ebead et al. had reported in the synthesis and the UV-Visible solvatochromism combined with semiempirical calculations to study the tautomerism of 1,3-benzothiazol-2-ylacetonitrile azo dyes [1]. In this study, 1,3-ben zothiazol-2-ylacetonitrile azo dyes (1-6) have been resynthesized, one and two dimensional H-1 and C-13 NMR, as well as absorption and emission spectra, were collected and interpreted. The obtained results were used to clarify the tautomerization phenomenon of these dyes. Predominantly, these dyes exist in Z-hydrazone form reinforced through intramolecular hydrogen bonding in deuterated chloroform. Substituents (R) in carbon7 (CR7) are the key player of the changes in H-1 and C-13 NMR chemical shifts, also in the absorption and emission wavelengths of benzothiazole azo dyes. Also, the relative photoluminescence quantum yields (PL QY) of these dyes (1-6) were estimated and related to the nature of substituents. Finally, PM6 semiempirical calculations were employed to confirm the preferred geometric structure and experimental NMR, absorption, and emission results.
|
|
| 10. |
- Leard, Lorriana E., et al.
(author)
-
Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation
- 2021
-
In: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498 .- 1557-3117. ; 40, s. 1349-1379
-
Journal article (peer-reviewed)abstract
- Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.
|
|
| 11. |
- Mosaad, Zienab, et al.
(author)
-
Emergence of Highly Pathogenic Avian Influenza A Virus (H5N1) of Clade 2.3.4.4b in Egypt, 2021-2022
- 2023
-
In: Pathogens. - : MDPI. - 2076-0817. ; 12:1
-
Journal article (peer-reviewed)abstract
- Wild migratory birds have the capability to spread avian influenza virus (AIV) over long distances as well as transmit the virus to domestic birds. In this study, swab and tissue samples were obtained from 190 migratory birds during close surveillance in Egypt in response to the recent outbreaks of the highly pathogenic avian influenza (HPAI) H5N1 virus. The collected samples were tested for a variety of AIV subtypes (H5N1, H9N2, H5N8, and H6N2) as well as other pathogens such as NDV, IBV, ILT, IBDV, and WNV. Among all of the tested samples, the HPAI H5N1 virus was found in six samples; the other samples were found to be negative for all of the tested pathogens. The Egyptian HPAI H5N1 strains shared genetic traits with the HPAI H5N1 strains that are currently being reported in Europe, North America, Asia, and Africa in 2021-2022. Whole genome sequencing revealed markers associated with mammalian adaption and virulence traits among different gene segments, similar to those found in HPAI H5N1 strains detected in Europe and Africa. The detection of the HPAI H5N1 strain of clade 2.3.4.4b in wild birds in Egypt underlines the risk of the introduction of this strain into the local poultry population. Hence, there is reason to be vigilant and continue epidemiological and molecular monitoring of the AIV in close proximity to the domestic-wild bird interface.
|
|
| 12. |
- Biffi, Alessandro, et al.
(author)
-
APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study
- 2011
-
In: Lancet Neurology. - 1474-4465. ; 10:8, s. 702-709
-
Journal article (peer-reviewed)abstract
- Background Carriers of APOE epsilon 2 and epsilon 4 have an increased risk of intracerebral haemorrhage (ICH) in lobar regions, presumably because of the effects of these gene variants on risk of cerebral amyloid angiopathy. We aimed to assess whether these variants also associate with severity of ICH, in terms of haematoma volume at presentation and subsequent outcome. Methods We investigated the association of APOE epsilon 2 and epsilon 4 with ICH volume and outcomes in patients with primary ICH in three phases: a discovery phase of 865 individuals of European ancestry from the Genetics of Cerebral Hemorrhage on Anticoagulation study, and replication phases of 946 Europeans (replication 1) and 214 African-Americans (replication 2) from an additional six studies. We also assessed the association of APOE variants with ICH volume and outcomes in meta-analyses of results from all three phases, and the association of APOE epsilon 4 with mortality in a further meta-analysis including data from previous reports. Admission ICH volume was quantified on CT scan. We assessed functional outcome (modified Rankin scale score 3-6) and mortality at 90 days. We used linear regression to establish the effect of genotype on haematoma volume and logistic regression to assess the effect on outcome from ICH. Findings For patients with lobar ICH, carriers of the APOE epsilon 2 allele had larger ICH volumes than did non-carriers in the discovery phase (p=2. 5x10(-5)), in both replication phases (p=0.008 in Europeans and p=0.016 in African-Americans), and in the meta-analysis (p=3.2x10(-8)). In the meta-analysis, each copy of APOE epsilon 2 increased haematoma size by a mean of 5.3 mL (95% CI 4.7-5.9; p=0.004). Carriers of APOE epsilon 2 had increased mortality (odds ratio [OR] 1.50, 95% CI 1.23-1.82; p=2.45x10(-5)) and poorer functional outcomes (modified Rankin scale score 3-6; 1-52, 1.25-1.85; p=1.74x10(-5)) compared with non-carriers after lobar ICH. APOE epsilon 4 was not associated with lobar ICH volume, functional outcome, or mortality in the discovery phase, replication phases, or meta-analysis of these three phases; in our further meta-analysis of 2194 patients, this variant did not increase risk of mortality (1.08,0.86-1.36; p=0.52). APOE allele variants were not associated with deep ICH volume, functional outcome, or mortality. Interpretation Vasculopathic changes associated with the APOE epsilon 2 allele might have a role in the severity and clinical course of lobar ICH. Screening of patients who have ICH to identify the epsilon 2 variant might allow identification of those at increased risk of mortality and poor functional outcomes.
|
|
| 13. |
- Gau, Rémi, et al.
(author)
-
Brainhack : Developing a culture of open, inclusive, community-driven neuroscience
- 2021
-
In: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 109:11, s. 1769-1775
-
Journal article (peer-reviewed)abstract
- Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
|
|
| 14. |
- Woo, Daniel, et al.
(author)
-
Meta-Analysis of Genome-Wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage.
- 2014
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:4, s. 511-521
-
Journal article (peer-reviewed)abstract
- Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.
|
|
| 15. |
- Zanaty, Ali M., et al.
(author)
-
Avian influenza virus surveillance in migratory birds in Egypt revealed a novel reassortant H6N2 subtype
- 2019
-
In: Avian Research. - : Elsevier BV. - 2053-7166. ; 10:1
-
Journal article (peer-reviewed)abstract
- BackgroundAvian influenza viruses (AIVs) have been identified from more than 100 different species of wild birds around the globe. Wild migratory birds can act as potential spreaders for AIVs to domestic birds between different countries. Egypt is situated on important migratory flyways for wild birds between different continents. While much is known about circulation of zoonotic potential H5N1 and H9N2 AIVs in domestic poultry in Egypt, little is known about the pivotal role of migratory birds in the maintenance and transmission of the viruses in Egypt.MethodsTargeted AIV surveillance has been conducted in 2017 in different wetlands areas in Northern and Eastern Egypt.ResultsAIV of subtype H5 was detected in two bird species. In addition, a novel reassortant strain of the H6N2 subtype was identified which reveals the continuous risk of new influenza virus(es) introduction into Egypt. This novel virus possesses a reassortant pattern originating from different AIV gene pools.ConclusionsIntervention control strategies should be performed to minimize the possible contact of domestic birds with wild birds to lower the risk of virus transmission at this interface. In addition, constant monitoring of AIVs in migratory birds is essential in the early detection of influenza virus introduction into Egypt.
|
|
| 16. |
- Amer, Fatma, et al.
(author)
-
Temporal Dynamics of Influenza A(H5N1) Subtype before and after the Emergence of H5N8
- 2021
-
In: Viruses. - : MDPI. - 1999-4915. ; 13:8
-
Journal article (peer-reviewed)abstract
- Highly pathogenic avian influenza (HPAI) viruses continue to circulate worldwide, causing numerous outbreaks among bird species and severe public health concerns. H5N1 and H5N8 are the two most fundamental HPAI subtypes detected in birds in the last two decades. The two viruses may compete with each other while sharing the same host population and, thus, suppress the spread of one of the viruses. In this study, we performed a statistical analysis to investigate the temporal correlation of the HPAI H5N1 and HPAI H5N8 subtypes using globally reported data in 2015-2020. This was joined with an in-depth analysis using data generated via our national surveillance program in Egypt. A total of 6412 outbreaks were reported worldwide during this period, with 39% (2529) as H5N1 and 61% (3883) as H5N8. In Egypt, 65% of positive cases were found in backyards, while only 12% were found in farms and 23% in live bird markets. Overall, our findings depict a trade-off between the number of positive H5N1 and H5N8 samples around early 2017, which is suggestive of the potential replacement between the two subtypes. Further research is still required to elucidate the underpinning mechanisms of this competitive dynamic. This, in turn, will implicate the design of effective strategies for disease control.
|
|
| 17. |
- Bayha, Luca, et al.
(author)
-
Observing the emergence of a quantum phase transition shell by shell
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7835, s. 583-587
-
Journal article (peer-reviewed)abstract
- Many-body physics describes phenomena that cannot be understood by looking only at the constituents of a system1. Striking examples are broken symmetry, phase transitions and collective excitations2. To understand how such collective behaviour emerges as a system is gradually assembled from individual particles has been a goal in atomic, nuclear and solid-state physics for decades3–6. Here we observe the few-body precursor of a quantum phase transition from a normal to a superfluid phase. The transition is signalled by the softening of the mode associated with amplitude vibrations of the order parameter, usually referred to as a Higgs mode7. We achieve fine control over ultracold fermions confined to two-dimensional harmonic potentials and prepare closed-shell configurations of 2, 6 and 12 fermionic atoms in the ground state with high fidelity. Spectroscopy is then performed on our mesoscopic system while tuning the pair energy from zero to a value larger than the shell spacing. Using full atom counting statistics, we find the lowest resonance to consist of coherently excited pairs only. The distinct non-monotonic interaction dependence of this many-body excitation, combined with comparison with numerical calculations allows us to identify it as the precursor of the Higgs mode. Our atomic simulator provides a way to study the emergence of collective phenomena and the thermodynamic limit, particle by particle.
|
|
| 18. |
- Devan, William J., et al.
(author)
-
Heritability Estimates Identify a Substantial Genetic Contribution to Risk and Outcome of Intracerebral Hemorrhage
- 2013
-
In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:6, s. 1578-1583
-
Journal article (peer-reviewed)abstract
- Background and Purpose-Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods-We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. Results-ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOE loci and at 12% (SE, 4%) for APOE. Conclusions-Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified.
|
|
| 19. |
- El-Saadony, Mohamed T., et al.
(author)
-
Impacts of turmeric and its principal bioactive curcumin on human health: pharmaceutical, medicinal, and food applications : a comprehensive review
- 2023
-
In: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
-
Research review (peer-reviewed)abstract
- The yellow polyphenolic pigment known as curcumin, originating from the rhizome of the turmeric plant Curcuma longa L., has been utilized for ages in ancient medicine, as well as in cooking and food coloring. Recently, the biological activities of turmeric and curcumin have been thoroughly investigated. The studies mainly focused on their antioxidant, antitumor, anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective impacts. This review seeks to provide an in-depth, detailed discussion of curcumin usage within the food processing industries and its effect on health support and disease prevention. Curcumin’s bioavailability, bio-efficacy, and bio-safety characteristics, as well as its side effects and quality standards, are also discussed. Finally, curcumin’s multifaceted uses, food appeal enhancement, agro-industrial techniques counteracting its instability and low bioavailability, nanotechnology and focused drug delivery systems to increase its bioavailability, and prospective clinical use tactics are all discussed.
|
|
| 20. |
|
|
| 21. |
- Falcone, Guido J., et al.
(author)
-
Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage
- 2012
-
In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 43:11, s. 2877-2883
-
Journal article (peer-reviewed)abstract
- Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN. (Stroke. 2012; 43: 2877-2883.)
|
|
| 22. |
|
|
| 23. |
- Khan, N. A., et al.
(author)
-
Patient's global assessment of disease activity and patient's assessment of general health for rheumatoid arthritis activity assessment : Are they equivalent?
- 2012
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71:12, s. 1942-1949
-
Journal article (peer-reviewed)abstract
- Objectives: To assess (A) determinants of patient's global assessment of disease activity (PTGL) and patient's assessment of general health (GH) scores of rheumatoid arthritis (RA) patients; (B) whether they are equivalent as individual variables; and (C) whether they may be used interchangeably in calculating common RA activity assessment composite indices. Methods: Data of 7023 patients from 30 countries in the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) was analysed. PTGL and GH determinants were assessed by mixed-effects analyses of covariance models. PTGL and GH equivalence was determined by Bland-Altman 95% limits of agreement (BALOA) and Lin's coefficient of concordance (LCC). Concordance between PTGL and GH based Disease Activity Score 28(DAS28), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) indices were calculated using LCC, and the level of agreement in classifying RA activity in four states (remission, low, moderate, high) using κ statistics. Results: Significant differences in relative and absolute contribution of RA and non-RA related variables in PTGL and GH ratings were noted. LCC of 0.64 and BALOA of -4.41 to 4.54 showed that PTGL and GH are not equivalent. There was excellent concordance (LCC 0.95-0.99) for PTGL and GH based DAS28, CDAI and RAPID3 indices, and >80% absolute agreement (κ statistics 0.75-0.84) in RA activity state classification for all three indices. Conclusions: PTGL and GH ratings differ in their determinants. Although they are individually not equivalent, they may be used interchangeably for calculating composite indices for RA activity assessment.
|
|
| 24. |
- Marini, Sandro, et al.
(author)
-
17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage
- 2018
-
In: Stroke. - 0039-2499. ; 49:7, s. 1618-1625
-
Journal article (peer-reviewed)abstract
- Background and Purpose-Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. Methods-We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-Assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with P<5×10- 8 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively. Results-The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: A genomic region on 22q13 encompassing PARVB (top single-nucleotide polymorphism rs9614326: β, 1.84; SE, 0.32; P=4.4×10-8) for lobar ICH volume and an intergenic region overlying numerous copy number variants on 17p12 (top single-nucleotide polymorphism rs11655160: β, 0.95; SE, 0.17; P=4.3×10-8) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for 17p12 (P=0.04; meta-Analysis P=2.5×10-9; heterogeneity, P=0.16) but not for 22q13 (P=0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; P=0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; P=0.045). Conclusions-We identified 17p12 as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association.
|
|
| 25. |
- Rannikmaee, Kristiina, et al.
(author)
-
Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease
- 2015
-
In: Neurology. - 1526-632X. ; 84:9, s. 918-926
-
Journal article (peer-reviewed)abstract
- Objectives:We hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease.Methods:We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084).Results:Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r(2) > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes.Conclusions:Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.
|
|
