Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular ...cells in humans. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult human cerebrovasculature, including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. By leveraging this reference, we investigated cellular and molecular perturbations in brain arteriovenous malformations, which are a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. We illustrate the interplay between vascular and immune cells that contributes to brain hemorrhage and catalog opportunities for targeting angiogenic and inflammatory programs in vascular malformations.
Promoting Islam as a defender of human rights is laden with difficulties. Advocates of human rights will readily point out numerous humanitarian failures carried out in the name of Islam. InThe ...Rights of God, Irene Oh looks at human rights and Islam as a religious issue rather than a political or legal one and draws on three revered Islamic scholars to offer a broad range of perspectives that challenge our assumptions about the role of religion in human rights. The theoretical shift from the conception of morality based in natural duty and law to one of rights has created tensions that hinder a fruitful exchange between human rights theorists and religious thinkers. Does the static identification of human rights with lists of specific rights, such as those found in the Universal Declaration of Human Rights, make sense given the cultural, historical, and religious diversity of the societies in which these rights are to be respected and implemented? In examining human rights issues of the contemporary Islamic world, Oh illustrates how the value of religious scholarship cannot be overestimated. Oh analyzes the commentaries of Abul A'la Maududi, Sayyid Qutb, and Abdolkarim Soroush-all prominent and often controversial Islamic thinkers-on the topics of political participation, religious toleration, and freedom of conscience. While Maududi and Qutb represent traditional Islam, and Soroush a more reform and Western-friendly approach, all three contend that Islam is indeed capable of accommodating and advocating human rights. Whereas disentangling politics and culture from religion is never easy, Oh shows that the attempt must be made in order to understand and overcome the historical obstacles that prevent genuine dialogue from taking place across religious and cultural boundaries.
Objectives: To assess the effects of intrathecal baclofen (ITB) therapy for the treatment of poststroke spastic hemiparesis on quality of life, functional independence, and upper, lower extremity ...(UE, LE) motor functions.
Materials and Methods: Prospective observational study of adult men and women with a minimum 6‐month stroke‐related spastic hemiparesis graded as ≥2 in UE and LE on Modified Ashworth Scale (MAS). Patients served as their own controls with measures compared pre‐implant with 12 months post ITB including: MAS, manual muscle test (MMT), gait distance/velocity, Functional Independence Measures (FIM), stroke‐specific quality of life scale (SSQL), and upper extremity manual activity log.
Results: After 12‐month ITB therapy, 26 patients (poststroke = 6.4 ± 9 years) demonstrated 1) reduced MAS/increased MMT for most LE muscle groups (p≤ 0.0001); 2) reduced MAS/increased MMT most UE muscle groups (p≤ 0.01); 3) FIM scores improved (p≤ 0.05) except bed mobility and lower body dressing; 4) gait distance and velocity improved (p≤ 0.05); 5) SSQL domains of family roles, mobility, personality, self‐care, social roles, thinking, UE function, and work/productivity improved (p≤ 0.05); 6) amount of use and quality of movement of the spastic UE in performing common activities of daily living increased (p < 0.0001).
Conclusions: Regardless of duration of spastic hemiparesis, a reduction in tone with ITB therapy facilitates motor strength improvement and is associated with clinically significant improvements in functional independence and quality of life.
The human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are ...known to establish early brain regions and cortical areas, but how early patterns result in finer and more discrete spatial differences remains poorly understood
. Here we use single-cell RNA sequencing to profile ten major brain structures and six neocortical areas during peak neurogenesis and early gliogenesis. Within the neocortex, we find that early in the second trimester, a large number of genes are differentially expressed across distinct cortical areas in all cell types, including radial glia, the neural progenitors of the cortex. However, the abundance of areal transcriptomic signatures increases as radial glia differentiate into intermediate progenitor cells and ultimately give rise to excitatory neurons. Using an automated, multiplexed single-molecule fluorescent in situ hybridization approach, we find that laminar gene-expression patterns are highly dynamic across cortical regions. Together, our data suggest that early cortical areal patterning is defined by strong, mutually exclusive frontal and occipital gene-expression signatures, with resulting gradients giving rise to the specification of areas between these two poles throughout successive developmental timepoints.
Volatile anesthetics (VAs) alter the function of key central nervous system proteins but it is not clear which, if any, of these targets mediates the immobility produced by VAs in the face of noxious ...stimulation. A leading candidate is the glycine receptor, a ligand-gated ion channel important for spinal physiology. VAs variously enhance such function, and blockade of spinal glycine receptors with strychnine affects the minimal alveolar concentration (an anesthetic EC50) in proportion to the degree of enhancement.
We produced single amino acid mutations into the glycine receptor α1 subunit that increased (M287L, third transmembrane region) or decreased (Q266I, second transmembrane region) sensitivity to isoflurane in recombinant receptors, and introduced such receptors into mice. The resulting knockin mice presented impaired glycinergic transmission, but heterozygous animals survived to adulthood, and we determined the effect of isoflurane on glycine-evoked responses of brainstem neurons from the knockin mice, and the minimal alveolar concentration for isoflurane and other VAs in the immature and mature knockin mice.
Studies of glycine-evoked currents in brainstem neurons from knockin mice confirmed the changes seen with recombinant receptors. No increases in the minimal alveolar concentration were found in knockin mice, but the minimal alveolar concentration for isoflurane and enflurane (but not halothane) decreased in 2-week-old Q266I mice. This change is opposite to the one expected for a mutation that decreases the sensitivity to volatile anesthetics.
Taken together, these results indicate that glycine receptors containing the α1 subunit are not likely to be crucial for the action of isoflurane and other VAs.
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