Is There a Difference in Clinical Measures and Structural Magnetic Resonance Imaging Metrics Between Minor Stroke and Migraine Patients?

Background: Patients presenting with minor acute focal neurological symptoms are often diagnosed with minor stroke, transient ischaemic attack, or migraine. Early diagnosis and treatment, in the case of the first two, is important to reduce risk of major strokes. The aim of this study was to assess whether there was a difference in clinical measures and structural magnetic resonance imaging (MRI) metrics between minor stroke and migraine patients. Methods: Twenty-two minor stroke (54.2 ±13.8 years; 10:12 female:male) and twenty-four migraine patients (44.2 ±13.0 years; 12:12 female:male) were enrolled. Clinical measures and structural MRI metrics, the latter extracted with FreeSurfer, were analysed using t test, Pearson correlation coefficient and ordinal regression in SPSS, version 26. The Benjamini-Hochberg post-hoc analysis, with FDR of 0.05, was applied for the t tests and correlations. Results: Systolic (p=0.001, t=3.774), mean arterial (p=0.002, t=3.348), diastolic blood pressure (p=0.009, t=2.721) and pulse pressure (p=0.003, t=3.207) were higher in minor stroke compared to migraine. Grey matter hyperintensities (p=0.002, t=3.350), white matter hyperintensities (p=0.018, t=2.462) and total Scheltens Score (p=0.013, t=2.580) were higher in minor stroke compared to migraine. Left (p=0.007, t=-2.389), right (p=0.009, t=-2.722) and total (p=0.007, t=-2.815) cortical thickness were higher in migraine compared to minor stroke. A significant correlation was observed between pulse pressure and total Scheltens score (r=0.653, p=0.001) in migraine patients. Ordinal regression showed an association between increased age and minor stroke with an odds ratio of 0.948 (95% CI, 0.902-0.996), Wald χ2 (1) = 4.449 p=0.034. Conclusion: The minor stroke results are consistent with current literature. The increased cortical thickness in migraine, could possibly be linked to the cortical spreading theory. This finding and the significant positive correlation between pulse pressure and Scheltens score in migraine warrant further investigation

Rehabilitation needs for older adults with stroke living at home: perceptions of four populations

<p>Abstract</p> <p>Background</p> <p>Many people who have suffered a stroke require rehabilitation to help them resume their previous activities and roles in their own environment, but only some of them receive inpatient or even outpatient rehabilitation services. Partial and unmet rehabilitation needs may ultimately lead to a loss of functional autonomy, which increases utilization of health services, number of hospitalizations and early institutionalization, leading to a significant psychological and financial burden on the patients, their families and the health care system. The aim of this study was to explore partially met and unmet rehabilitation needs of older adults who had suffered a stroke and who live in the community. The emphasis was put on needs that act as obstacles to social participation in terms of personal factors, environmental factors and life habits, from the point of view of four target populations.</p> <p>Methods</p> <p>Using the focus group technique, we met four types of experts living in three geographic areas of the province of Québec (Canada): older people with stroke, caregivers, health professionals and health care managers, for a total of 12 groups and 72 participants. The audio recordings of the meetings were transcribed and NVivo software was used to manage the data. The process of reducing, categorizing and analyzing the data was conducted using themes from the Disability Creation Process model.</p> <p>Results</p> <p>Rehabilitation needs persist for nine capabilities (e.g. related to behaviour or motor activities), nine factors related to the environment (e.g. type of teaching, adaptation and rehabilitation) and 11 life habits (e.g. nutrition, interpersonal relationships). The caregivers and health professionals identified more unmet needs and insisted on an individualized rehabilitation. Older people with stroke and the health care managers had a more global view of rehabilitation needs and emphasized the availability of resources.</p> <p>Conclusion</p> <p>Better knowledge of partially met or unmet rehabilitation needs expressed by the different types of people involved should lead to increased attention being paid to education for caregivers, orientation of caregivers towards resources in the community, and follow-up of patients' needs in terms of adjustment and rehabilitation, whether for improving their skills or for carrying out their activities of daily living.</p

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The European Modern Pollen Database (EMPD) project

Modern pollen samples provide an invaluable research tool for helping to interpret the quaternary fossil pollen record, allowing investigation of the relationship between pollen as the proxy and the environmental parameters such as vegetation, land-use, and climate that the pollen proxy represents. The European Modern Pollen Database (EMPD) is a new initiative within the European Pollen Database (EPD) to establish a publicly accessible repository of modern (surface sample) pollen data. This new database will complement the EPD, which at present holds only fossil sedimentary pollen data. The EMPD is freely available online to the scientific community and currently has information on almost 5,000 pollen samples from throughout the Euro-Siberian and Mediterranean regions, contributed by over 40 individuals and research groups. Here we describe how the EMPD was constructed, the various tables and their fields, problems and errors, quality controls, and continuing efforts to improve the available data