Culture of Human Retinal Explants for Ex Vivo Assessment of AAV Gene Delivery.

Due to the clinically established safety and efficacy profile of recombinant adeno-associated viral (rAAV) vectors, they are considered the "go to" vector for retinal gene therapy. Design of a rAAV-mediated gene therapy focuses on cell tropism, high transduction efficiency, and high transgene expression levels to achieve the lowest therapeutic treatment dosage and avoid toxicity. Human retinal explants are a clinically relevant model system for exploring these aspects of rAAV-mediated gene delivery.

Generation of Human iPSC-Derived Retinal Organoids for Assessment of AAV-Mediated Gene Delivery.

Human retinal organoids derived from induced pluripotent stem cells (iPSCs) serve as a promising preclinical model for testing the safety and efficacy of viral gene therapy. Retinal organoids recapitulate the stratified multilayered epithelium structure of the developing and maturating human retina. As such, retinal organoids are unique tools to model retinal disease and to test therapeutic interventions toward their amelioration.

Machine phenotyping of cluster headache and its response to verapamil.

Cluster headache is characterized by recurrent, unilateral attacks of excruciating pain associated with ipsilateral cranial autonomic symptoms. Although a wide array of clinical, anatomical, physiological, and genetic data have informed multiple theories about the underlying pathophysiology, the lack of a comprehensive mechanistic understanding has inhibited, on the one hand, the development of new treatments and, on the other, the identification of features predictive of response to established ones. The first-line drug, verapamil, is found to be effective in only half of all patients, and after several weeks of dose escalation, rendering therapeutic selection both uncertain and slow.

Noninvasive Vagus Nerve Stimulation for Treatment of Indomethacin-Sensitive Headaches.

This study examines the effectiveness of transcutaneous stimulation of the vagus nerve for trigeminal autonomic cephalalgias.

Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention?

Migraine is a very disabling disorder with severe impact on patients' lives and substantive costs to society in terms of healthcare costs and lost productivity. Prevention is a key component of migraine therapy, and while numerous preventive options exist, each is burdened by either troublesome side effects or insufficient efficacy. All migraine preventives currently in clinical use were licensed for other purposes and, by chance, have efficacy against migraine.

Increased rate of venous thrombosis may be associated with inpatient dihydroergotamine treatment.

Objective: To review whether the incidence of catheter-associated venous thromboses was higher in patients receiving IV dihydroergotamine compared to lidocaine.

Methods: We retrospectively reviewed all admissions at the University of California, San Francisco Headache Center from February 25, 2008, through October 31, 2014, for age, sex, diagnosis, aura, treatment dose, type of IV line used, days with line, superficial (SVT) or deep venous thrombosis (DVT), and pulmonary embolism (PE).

Results: A peripherally inserted central catheter (PICC) or midline catheter was placed in 315 of 589 (53%) admissions.

Aprepitant for the management of nausea with inpatient IV dihydroergotamine.

Objective: To assess the efficacy and tolerability of oral aprepitant, a substance P/neurokinin A receptor antagonist, in controlling nausea associated with IV dihydroergotamine (DHE) administered for medically refractory migrainous headache in patients not responding to standard antiemetics or with a history of uncontrolled nausea with DHE.

Methods: This was a retrospective chart review of prospectively collected hourly diary data and clinical notes of patients hospitalized between 2011 and 2015 for inpatient treatment with DHE. Patients were classified using the International Classification of Headache Disorders, 3rd edition (beta version).

Headache.

Headache disorders are primarily managed in an outpatient setting; therefore, the authors focus on the primary headache disorders that comprise the bulk of clinical practice. Red flags for secondary headaches that may be more commonly encountered in clinic are briefly discussed.

InSPAL: A Novel Immersive Virtual Learning Programme.

In this paper we introduce The Interactive Sensory Program for Affective Learning (InSPAL) a pioneering virtual learning programme designed for the severely intellectually disabled (SID) students, who are having cognitive deficiencies and other sensory-motor handicaps, and thus need more help and attention in overcoming their learning difficulties. Through combining and integrating interactive media and virtual reality technology with the principles of art therapy and relevant pedagogical techniques, InSPAL aims to strengthen SID students' pre-learning abilities, promote their self-awareness, decrease behavioral interferences with learning as well as social interaction, enhance their communication and thus promote their quality of life. Results of our study show that students who went through our programme were more focused, and the ability to do things more independently increased by 15%.

Morphological Abnormalities of Thalamic Subnuclei in Migraine: A Multicenter MRI Study at 3 Tesla.

Unlabelled: The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine.

Recent neuroimaging advances in the study of primary headaches.

Neuroimaging techniques can be used to investigate both functional and structural features of the brain in patients who have primary headache disorders such as migraine or cluster headache. Improved treatments are needed for both, and this goal will likely be facilitated by a better understanding of the underlying biology. Functional imaging studies have identified regions active during attacks, as well as abnormalities that are present during the interictal period.

The anterior insula shows heightened interictal intrinsic connectivity in migraine without aura.

Objective: We sought to explore whether patients with migraine show heightened interictal intrinsic connectivity within primary sensory networks, the salience network, and a network anchored by the dorsal pons, a region known to be active during migraine attacks.

Methods: Using task-free fMRI and a region-of-interest analysis, we compared intrinsic connectivity patterns in 15 migraineurs without aura to 15 age- and sex-matched healthy controls, focusing on networks anchored by the calcarine cortex, Heschl gyrus, right anterior insula, and dorsal pons, a region active during migraine attacks. We also examined the relationship between network connectivity, migraine frequency, and sensory sensitivity symptoms.

New targets for migraine therapy.

The shift in our understanding of migraine as a vascular disorder to a brain disorder has opened new avenues for the development of novel therapeutics with neural targets. The advent of 5-HT1B/1D receptor agonists, the triptans, in the 1990s was a crucial step in the modern evolution of treatment. The use of triptans, like their predecessors, is limited by their vasoconstrictor effects, and new development has been slowed by poor academic research funding to identify new targets.

Interleukin-6 174G/C polymorphism and ischemic stroke: a systematic review.

Background And Purpose: Interleukin-6 (IL-6) is associated with atherosclerotic disease and is also a key mediator in the inflammatory response to cerebral ischemia. Although the IL-6 -174G/C promoter polymorphism has been associated with carotid artery atherosclerosis and coronary heart disease, its relation to ischemic stroke is unclear. This review summarizes the current literature and discusses methodological considerations for future studies.