scholarly journals Beyond the Brain

Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 3007-3017
Author(s):  
Kristiina Rannikmäe ◽  
David E. Henshall ◽  
Sophie Thrippleton ◽  
Qiu Ginj Kong ◽  
Mike Chong ◽  
...  
Keyword(s):  
Transient Ischemic Attack ◽  
Large Scale ◽  
Small Vessel Disease ◽  
Population Based ◽  
Pathogenic Variant ◽  
Pathogenic Variants ◽  
Scale Population ◽  
Underlying Mechanisms ◽  
Ischemic Attack ◽  
Meta Analyses

Background and Purpose: An important minority of cerebral small vessel disease (cSVD) is monogenic. Many monogenic cSVD genes are recognized to be associated with extracerebral phenotypes. We assessed the frequency of these phenotypes in existing literature. Methods: We performed a systematic review following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), searching Medline/Embase for publications describing individuals with pathogenic variants in COL4A1/2 , TREX1 , HTRA1 , ADA2 , and CTSA genes (PROSPERO 74804). We included any publication reporting on ≥1 individual with a pathogenic variant and their clinically relevant phenotype. We extracted individuals’ characteristics and information about associated extracerebral phenotypes and stroke/transient ischemic attack. We noted any novel extracerebral phenotypes and looked for shared phenotypes between monogenic cSVDs. Results: After screening 6048 publications, we included 96 COL4A1 (350 individuals), 32 TREX1 (115 individuals), 43 HTRA1 (38 homozygous/61 heterozygous individuals), 16 COL4A2 (37 individuals), 119 ADA2 (209 individuals), and 3 CTSA (14 individuals) publications. The majority of individuals originated from Europe/North America, except for HTRA1 , where most were from Asia. Age varied widely, ADA2 individuals being youngest and heterozygous HTRA1/CTSA individuals oldest. Sex distribution appeared equal. Extracerebral phenotypes were common: 14% to 100% of individuals with a pathogenic variant manifested at least one extracerebral phenotype (14% COL4A2 , 43% HTRA1 heterozygotes, 47% COL4A1 , 57% TREX1 , 91% ADA2 , 94% HTRA1 homozygotes, and 100% CTSA individuals). Indeed, for 4 of 7 genes, an extracerebral phenotype was observed more frequently than stroke/transient ischemic attack. Ocular, renal, hepatic, muscle, and hematologic systems were each involved in more than one monogenic cSVD. Conclusions: Extracerebral phenotypes are common in monogenic cSVD with extracerebral system involvement shared between genes. However, inherent biases in the existing literature mean that further data from large-scale population-based longitudinal studies collecting health outcomes in a systematic unbiased way is warranted. The emerging knowledge will help to select patients for testing, inform clinical management, and provide further insights into the underlying mechanisms of cSVD.

scholarly journals Ancestrally and Temporally Diverse Analysis of Penetrance of Clinical Variants in 72,434 Individuals

2021 ◽  
Author(s):  
Iain S. Forrest ◽  
Kumardeep Chaudhary ◽  
Ha My T. Vy ◽  
Shantanu Bafna ◽  
Daniel M. Jordan ◽  
...  
Keyword(s):  
Large Scale ◽  
Disease Risk ◽  
Sequence Data ◽  
Genomic Medicine ◽  
Population Based ◽  
Loss Of Function ◽  
Pathogenic Variants ◽  
Scale Population ◽  
Predisposition Genes ◽  
Disease Predisposition

ABSTRACTA major goal of genomic medicine is to quantify the disease risk of genetic variants. Here, we report the penetrance of 37,772 clinically relevant variants (including those reported in ClinVar1 and of loss-of-function consequence) for 197 diseases in an analysis of exome sequence data for 72,434 individuals over five ancestries and six decades of ages from two large-scale population-based biobanks (BioMe Biobank and UK Biobank). With a high-quality set of 5,359 clinically impactful variants, we evaluate disease prevalence in carriers and non-carriers to interrogate major determinants and implications of penetrance. First, we associate biomarker levels with penetrance of variants in known disease-predisposition genes and illustrate their clear biological link to disease. We then systematically uncover large numbers of ClinVar pathogenic variants that confer low risk of disease, even among those reviewed by experts, while delineating stark differences in variant penetrance by molecular consequence. Furthermore, we ascertain numerous variants present in non-European ancestries and reveal how increasing carrier age modifies penetrance estimates. Lastly, we examine substantial heterogeneity of penetrance among variants in known disease-predisposition genes for conditions such as familial hypercholesterolemia and breast cancer. These data indicate that existing categorical systems for variant classification do not adequately capture disease risk and warrant consideration of a more quantitative system based on population-based penetrance to evaluate clinical impact.

scholarly journals Publisher Correction: A link between appendectomy and gastrointestinal cancers: a large-scale population-based cohort study in Korea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Youn Young Park ◽  
Kil‑yong Lee ◽  
Seong Taek Oh ◽  
Sang Hyun Park ◽  
Kyung Do Han ◽  
...  
Keyword(s):  
Cohort Study ◽  
Large Scale ◽  
Population Based ◽  
Gastrointestinal Cancers ◽  
Scale Population

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Maternal adherence to micronutrient supplementation before and during pregnancy in Northwest China: a large-scale population-based cross-sectional survey

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e028843 ◽  
Author(s):  
Danmeng Liu ◽  
Yue Cheng ◽  
Shaonong Dang ◽  
Duolao Wang ◽  
Yaling Zhao ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Large Scale ◽  
Northwest China ◽  
Population Based ◽  
Shaanxi Province ◽  
Micronutrient Supplementation ◽  
Cross Sectional Survey ◽  
Start Time ◽  
Cross Sectional ◽  
Scale Population

ObjectivesTo report the situation of maternal micronutrient supplementation before and during pregnancy in Northwest China and to examine the rates of and factors related to the adherence to micronutrient supplementation among pregnant women in this region, where dietary micronutrient intake is commonly insufficient.DesignA large-scale population-based cross-sectional survey.SettingTwenty counties and ten districts of Shaanxi Province.ParticipantsA sample of 30 027 women were selected using a stratified multistage random sampling method. A total of 28 678 women were chosen for the final analysis after excluding those who did not provide clear information about nutritional supplementation before and during pregnancy.Main outcome measuresMaternal adherence to micronutrient supplementation (high and low) were the outcomes. They were determined by the start time and duration of use according to Chinese guidelines (for folic acid (FA) supplements) and WHO recommendations (for iron, calcium and multiple-micronutrient (MMN) supplements).ResultsIn total, 83.9% of women took at least one kind of micronutrient supplement before or during pregnancy. FA (67.6%) and calcium (57.5%) were the primarily used micronutrient supplements; few participants used MMN (14.0%) or iron (5.4%). Adherence to supplementation of all micronutrients was low (7.4% for FA, 0.6% for iron, 11.7% for calcium and 2.7% for MMN). Higher educational levels, higher income levels, urban residence and better antenatal care (including pregnancy consultation and a higher frequency of antenatal visits) were associated with high adherence to micronutrient supplementation.ConclusionMaternal micronutrient supplementation before and during pregnancy in Northwest China was way below standards recommended by the Chinese guidelines or WHO. Targeted health education and future nutritional guidelines are suggested to improve this situation, especially in pregnant women with disadvantaged sociodemographic conditions.

scholarly journals Increased Risk of Traffic Injury After a Cerebrovascular Event

Stroke ◽  
2018 ◽  
Vol 49 (12) ◽  
pp. 3006-3011
Author(s):  
Amy Y.X. Yu ◽  
Moira K. Kapral ◽  
Jiming Fang ◽  
Donald A. Redelmeier
Keyword(s):  
Transient Ischemic Attack ◽  
Motor Vehicle ◽  
Population Based ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Cerebrovascular Event ◽  
Traffic Injury ◽  
Increased Risk ◽  
Ischemic Attack ◽  
Serious Injuries

Background and Purpose— We aimed to determine the long-term risks of a motor vehicle collision after a cerebrovascular event and whether the risks were similar after left- or right-hemispheric events. Methods— We used a population-based registry to identify patients diagnosed with a transient ischemic attack or stroke (hemorrhagic or ischemic) between 2003 and 2013 in Ontario, Canada. Hemispheric laterality was determined using radiological and clinical findings. We identified subsequent serious injuries involving the patient as a driver using linked administrative data. Secondary outcomes included serious injuries involving the patient as a pedestrian, as a passenger, or other traumatic events (fall, fracture, ankle sprain). We used proportional hazard models accounting for death as a competing risk to test the association of hemispheric laterality and outcomes with and without adjustment for age, sex, discharge modified Rankin Scale score, home location, and prior driving record. Patients were followed through to 2017. Results— Among 26 144 patients with hemispheric cerebrovascular events, 377 subsequent serious traffic injuries as a driver (2.2 per 1000 person-year) were identified over a median follow-up of 6.4 person-years. The rate did not differ by laterality (adjusted hazard ratio, 1.00; 95% CI, 0.82–1.23). The risk of a serious traffic injury as a pedestrian was significantly higher after a right-sided than left-sided event (adjusted hazard ratio, 1.27; 95% CI, 1.02–1.58). Subsequent risks for other traumatic injuries did not differ by laterality of cerebrovascular event. Conclusions— The risk of a serious traffic injury as a pedestrian is substantially higher after a right-hemispheric cerebrovascular event compared with a left-sided event. Walking should be promoted for exercise in survivors of a stroke or transient ischemic attack, but these vulnerable road users may benefit from additional poststroke rehabilitation to optimize safety.

scholarly journals A Population-Based Study of Transient Ischemic Attack Incidence in Novosibirsk, Russia, 1987–1988 and 1996–1997

Stroke ◽  
2000 ◽  
Vol 31 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Valery L. Feigin ◽  
Sergey V. Shishkin ◽  
Georgii M. Tzirkin ◽  
Tatyana E. Vinogradova ◽  
Alexey V. Tarasov ◽  
...  
Keyword(s):  
Transient Ischemic Attack ◽  
Population Based ◽  
Population Based Study ◽  
Ischemic Attack

Activation Products of the Haemostatic System in Coronary, Cerebrovascular and Peripheral Arterial Disease

2001 ◽  
Vol 85 (02) ◽  
pp. 234-239 ◽  
Author(s):  
M. L. Bots ◽  
F. Haverkate ◽  
P. Meijer ◽  
A. Hofman ◽  
C. Kluft ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Transient Ischemic Attack ◽  
Pressure Ratio ◽  
Arterial Disease ◽  
Population Based ◽  
Control Subjects ◽  
History Of ◽  
Ischemic Attack ◽  
Peripheral Arterial ◽  
D Dimer

SummaryTo determine the presence of a ‘hypercoagulable state’ as assessed by indices of thrombin and plasmin generation and of the amount of fibrin that is lysed, in patients with stable coronary, cerebral and peripheral arterial disease a population-based cross-sectional study was performed. From a population-based cohort comprising 7983 men and women aged 55 years and over, we randomly selected 127 subjects with a history of myocardial infarction, 124 with a history of stroke and/or transient ischemic attack, 131 patients with peripheral arterial disease and 263 control subjects in the same age group without arterial disease. Subjects using anticoagulant drugs were not selected. F1+2, TAT, and PAP were not associated with a history of cardiovascular events, nor with peripheral arterial disease. In contrast, positive associations were found for D-Dimer. Mean D-Dimer level was 40 μg/l (95% CI 35,44) in control subjects; 53 μg/l (47, 61) in those with a history of myocar-dial infarction and 51 μg/l (45, 58) in those with a history of stroke and or transient ischemic attack. D-Dimer increased gradually with increasing severity of peripheral atherosclerosis; a decrease in ankle/arm systolic blood pressure ratio of 0.1 was associated with an increase in D-Dimer of 3.9 μg/l (p<0.01). This was more pronounced in subjects with higher F1+2, TAT and PAP concentration. In conclusion, the markers of onset of coagulation F1+2, TAT and PAP are not associated with the presence of arterial disease, but increased levels of these markers are necessary for the positive association between D-Dimer and arterial disease.

Intolerance to environmental chemicals and sounds in irritable bowel syndrome: Explained by central sensitization?

2016 ◽  
Vol 23 (10) ◽  
pp. 1367-1377 ◽  
Author(s):  
Linnea Ståhlberg ◽  
Eva Palmquist ◽  
Steven Nordin
Keyword(s):  
Irritable Bowel Syndrome ◽  
Traumatic Stress ◽  
Large Scale ◽  
Population Based ◽  
Environmental Chemicals ◽  
Post Traumatic Stress ◽  
Scale Population ◽  
Post Traumatic ◽  
Irritable Bowel ◽  
Behavioral Disruptions

This study tested the hypotheses of irritable bowel syndrome showing (1) comorbidity with chemical and sound intolerance, other types of functionally somatic syndromes, and psychiatric disorders and (2) stronger than normal affective reactions to and behavioral disruptions from odorous/pungent chemicals and sounds in daily life. These hypotheses were tested by means of data from a large-scale population-based questionnaire study. The results showed comorbidity in irritable bowel syndrome with chemical and sound intolerance, fibromyalgia, migraine, post-traumatic stress disorder, generalized anxiety disorder, panic syndrome, and depression as well as strong reactions/disruptions from odorous/pungent chemicals and sounds in irritable bowel syndrome.

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