Pre-operative extracranial and intracranial EEG investigation in patients with temporal lobe epilepsy: trends, results and review of pathophysiologic mechanisms

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66297/1/j.1600-0404.1988.tb08004.x.pd

Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD

Observational Study Design in Veterinary Pathology, Part 1: Study Design

Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods

Adaptation of a Couple-Based HIV Intervention for Methamphetamine-Involved African American Men who have Sex with Men

In the U.S., incidence of HIV infection among men who have sex with men (MSM) has steadily increased since the 1990s. This points to a need for innovation to address both emerging trends as well as longer-standing disparities in HIV risk and transmission among MSM, such as the elevated rates of HIV/STIs among African American MSM and methamphetamine users. While couple-based sexual risk reduction interventions are a promising avenue to reduce HIV/STI transmission, prior research has been almost exclusively with heterosexual couples. We sought to adapt an existing, evidence-based intervention—originally developed and tested with heterosexual couples—for a new target population consisting of African American MSM in a longer-term same-sex relationship where at least one partner uses methamphetamine. The adaptation process primarily drew from data obtained from a series of focus groups with 8 couples from the target population. Attention is given to the methods used to overcome challenges faced in this adaptation process: limited time, a lead investigator who is phenotypically different from the target population, a dearth of descriptive information on the experiences and worldviews among the target population, and a concomitant lack of topical experts. We also describe a visualization tool used to ensure that the adaptation process promotes and maintains adherence to the theory that guides the intervention and behavior change. The process culminated with an intervention adapted for the new target population as well as preliminary indications that a couple-based sexual-risk reduction intervention for African American, methamphetamine-involved male couples is feasible and attractive

Ablation of CaMKIId oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease

CRISPR-Cas9 gene editing is emerging as a prospective therapy for genomic mutations. However, current editing approaches are directed primarily toward relatively small cohorts of patients with specific mutations. Here, we describe a cardioprotective strategy potentially applicable to a broad range of patients with heart disease. We used base editing to ablate the oxidative activation sites of CaMKIId, a primary driver of cardiac disease. We show in cardiomyocytes derived from human induced pluripotent stem cells that editing the CaMKIId gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKIId editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKIId gene editing may thus represent a permanent and advanced strategy for heart disease therapy

Ethylene-mediated nitric oxide depletion pre-adapts plants to hypoxia stress

Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops

Single stage repair of a complex pathology: end stage ischaemic cardiomyopathy, ascending aortic aneurysm and thoracic coarctation

The not uncommon combination of ascending aortic pathology with late presenting coarctation is a difficult surgical challenge. The two stage approach is usually adopted. The necessity for cardiac transplantation adds to the complexity: a trans-sternal approach and single stage repair become mandatory

Coherent QCD phenomena in the Coherent Pion-Nucleon and Pion-Nucleus Production of Two Jets at High Relative Momenta

We use QCD to compute the cross section for coherent production of a di-jet (treated as a $q\bar q$ moving at high relative transverse momentum,$\kappa_t$). In the target rest frame,the space-time evolution of this reaction is dominated by the process in which the high $\kappa_t$ $q\bar q$ component of the pion wave function is formed before reaching the target. It then interacts through two gluon exchange. In the approximation of keeping the leading order in powers of $\alpha_s$ and all orders in $\alpha_{s}\ln(\kappa_{t}^2/k_{0}^2),$ the amplitudes for other processes are shown to be smaller at least by a power of $\alpha_{s}$. The resulting dominant amplitude is proportional to $z(1-z) \kappa_t^{-4}$ ($z$ is the fraction light-cone(+)momentum carried by the quark in the final state) times the skewed gluon distribution of the target. For the pion scattering by a nuclear target, this means that at fixed $x_{N}= 2\kappa_{t}^2/s$ (but $\kappa_{t}^2\to \infty$) the nuclear process in which there is only a single interaction is the most important one to contribute to the reaction. Thus in this limit color transparency phenomena should occur.These findings are in accord with E971 experiment at FNAL. We also re-examine a potentially important nuclear multiple scattering correction which is positive and $\propto A^{1/3}/\kappa_t^4$. The meaning of the signal obtained from the experimental measurement of pion diffraction into two jets is also critically examined and significant corrections are identified.We show also that for values of $\kappa_t$ achieved at fixed target energies, di-jet production by the e.m. field of the nucleus leads to an insignificant correction which gets more important as $\kappa_t$ increases.Comment: 23 pages, 9 figure

A consistent analysis of (e,e'p) and (d,3He) experiments

The apparent discrepancy between spectroscopic factors obtained in (e,e'p) and (d,3He) experiments is investigated. This is performed first for 48Ca(e,e'p) and 48Ca(d,3He) experiments and then for other nuclei. It is shown that the discrepancy disappears if the (d,3He) experiments are re-analyzed with a non-local finite range DWBA analysis with a bound-state wave function that is obtained from (e,e'p) experiments.Comment: 23 pages, 7 figure