The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Role of Soluble Epoxide Hydrolase in Postischemic Recovery of Heart Contractile Function

Cytochrome P450 epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) which are converted to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (Ephx2, sEH). To examine the functional role of sEH in the heart, mice with targeted disruption of the Ephx2 gene were studied. Hearts from sEH null mice have undetectable levels of sEH mRNA and protein and cannot convert EETs to DHETs. sEH null mice have normal heart anatomy and basal contractile function, but have higher fatty acid epoxide:diol ratios in plasma and cardiomyocyte cell culture media compared with wild type (WT). sEH null hearts have improved recovery of left ventricular developed pressure (LVDP) and less infarction compared with WT hearts after 20 minutes ischemia. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (10 to 100 nmol/L) before ischemia abolishes this cardioprotective phenotype. Inhibitor studies demonstrate that perfusion with phosphatidylinositol-3 kinase (PI3K) inhibitors wortmannin (200 nmol/L) or LY294002 (5 μmol/L), the ATP-sensitive K+ channel (KATP) inhibitor glibenclamide (1 μmol/L), the mitochondrial KATP (mitoKATP) inhibitor 5-hydroxydecanoate (100 to 200 μmol/L), or the Ca2+-sensitive K+ channel (KCa) inhibitor paxilline (10 μmol/L) abolishes the cardioprotection in sEH null hearts. Consistent with increased activation of the PI3K cascade, sEH null mice exhibit increased cardiac expression of glycogen synthase kinase-3β (GSK-3β) phospho-protein after ischemia. Together, these data suggest that targeted disruption of sEH increases the availability of cardioprotective EETs that work by activating PI3K signaling pathways and K+ channels

New fossil remains of Homo naledi from the Lesedi Chamber, South Africa

The Rising Star cave system has produced abundant fossil hominin remains within the Dinaledi Chamber, representing a minimum of 15 individuals attributed to Homo naledi. Further exploration led to the discovery of hominin material, now comprising 131 hominin specimens, within a second chamber, the Lesedi Chamber. The Lesedi Chamber is far separated from the Dinaledi Chamber within the Rising Star cave system, and represents a second depositional context for hominin remains. In each of three collection areas within the Lesedi Chamber, diagnostic skeletal material allows a clear attribution to H. naledi. Both adult and immature material is present. The hominin remains represent at least three individuals based upon duplication of elements, but more individuals are likely present based upon the spatial context. The most significant specimen is the near-complete cranium of a large individual, designated LES1, with an endocranial volume of approximately 610 ml and associated postcranial remains. The Lesedi Chamber skeletal sample extends our knowledge of the morphology and variation of H. naledi, and evidence of H. naledi from both recovery localities shows a consistent pattern of differentiation from other hominin species

Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood

Using a sample of children from the US Collaborative Perinatal Project, John McGrath and colleagues show that the offspring of older fathers exhibit subtle impairments on tests of neurocognitive ability during infancy and childhood

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

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

Intimate Partner Homicide: Using a 20-year national panel to identify patterns and prevalence

Background and significance: Lethal violence, including homicide and suicide, takes the lives of 45,000 Americans per year. Intimate partner ( IP) homicide is a type of lethal violence that is classified as a form of homicide by policymakers, law enforcement personnel, healthcare providers, and others. It accounts for only 7% of all homicides, but nearly one- third of all homicides of women. The rates of all types of lethal violence have decreased since 1985, but the distribution of IP homicide has gone from nearly half male and half female victims to one- quarter male and three- quarters female victims during that time. Because of the relationship shared between the perpetrator and the victim, the nearly unlimited access the perpetrator has to the victim, and the sociodemographic distinctions between IP homicide and non- intimate homicide, the author hypothesizes that it is not a type of homicide per se, but instead a separate entity deserving distinctively different approaches to prevent it. Design and Methods: The primary aim of this study is to determine if IP homicide is a type of homicide similar to non- intimate homicide in seasonal, regional, economic, and sociodemographic distributions, if it is more like suicide in those distributions, or if it a separate form of lethal violence with its own set of predictive criteria. The author of this study examines a comprehensive database consisting of homicide data from the Supplementary Homicide Reports, suicide data from the Mortality Multiple Cause of Death Reports, as well as Census, firearm, alcohol, and religiosity data from a variety of resources covering the entire United States from 1985- 2004. To create a panel for evaluation, the author aggregated these data at the county level to create a dataset with 54,037 county months of observations. Results: Intimate Partner Homicide does not correlate to regional, seasonal, economic, and sociodemographic variables in the same way as non- intimate homicide or suicide. Instead, IP Homicide does not vary with season or region of county. It does not correlate with increases in population density nationally, but does in the Northeast and the Midwest, where it has opposite correlations. Its only economic response is to negatively correlate with unemployment. Further, it is higher in counties with higher numbers of churchgoers. It also higher in counties with higher proportions of single-parent households and with broader age gaps between male and female intimates. The finding most important to policymakers is that since the passage of the Violence Against Women Act, IP homicide incidence has significantly decreased, but that decrease is disproportionately in favor of male victims. Discussion and Policy Implications: The results of this study support the post that Intimate Partner Homicide is a separate “ Current of Lethal Violence”, which many say is the most preventable type of lethal violence. Since IP homicide is not like non-intimate ( NI) homicide, it might not be amenable to the same prevention strategies applied to NI homicide. Examples of these strategies include an increased police presence in areas with higher IP homicide rates. Enhancements to the Violence Against Women Act that focuses on women not capable of taking risks to protect themselves, such as leaving the abuser, could prove very beneficial. These enhancements could include interventions focusing on education of mental health and emergency department healthcare providers, as well as improvements in law enforcement methods used to stop intimate violence. An approach that recognizes that IP homicide is unlike NI homicide; therefore, prevention should begin with recognition of the intimate dyad and its effect on the persons within it. Some couples might not want to be separated, but instead they might just want the violence to end

Intranasal monkeypox marmoset model: Prophylactic antibody treatment provides benefit against severe monkeypox virus disease.

Concerns regarding outbreaks of human monkeypox or the potential reintroduction of smallpox into an immunological naïve population have prompted the development of animal models and countermeasures. Here we present a marmoset model of monkeypox and smallpox disease utilizing a relevant poxvirus via a natural exposure route. We found that 1000 plaque forming units (PFU) of Monkeypox virus was sufficient to recapitulate smallpox disease, to include an incubation period of approximately 13 days, followed by the onset of rash, and death between 15 and 17 days. Temporally accurate manifestation of viremia and oral shedding were also features. The number of lesions ranged from no lesions to 299, the most reported in a marmoset exposed to a poxvirus. To both evaluate the efficacy of our antibodies and the applicability of the model system, marmosets were prophylactically treated with two monoclonal antibodies, c7D11 and c8A. Of three marmosets, two were completely free of disease and a single marmoset died 8 days after the mock (n = 1) or PBS control(s) (n = 2). Evaluation of the serum levels of the three animals provided a possible explanation to the animal succumbing to disease. Interestingly, more females had lesions (and a greater number of lesions) and lower viral burden (viremia and oral shedding) than males in our studies, suggesting a possible gender effect