CRISPR/Cas9-mediated mutagenesis of CAROTENOID CLEAVAGE DIOXYGENASE 8 in tomato provides resistance against the parasitic weed Phelipanche aegyptiaca.

Broomrapes (Phelipanche aegyptiaca and Orobanche spp.) are obligate plant parasites that cause extreme damage to crop plants. The parasite seeds have strict requirements for germination, involving preconditioning and exposure to specific chemicals strigolactones [SLs] exuded by the host roots. SLs are plant hormones derived from plant carotenoids via a pathway involving the Carotenoid Cleavage Dioxygenase 8 (CCD8). Having no effective means to control parasitic weeds in most crops, and with CRISPR/Cas9 being an effective gene-editing tool, here we demonstrate that CRISPR/Cas9-mediated mutagenesis of the CCD8 gene can be used to develop host resistance to the parasitic weed P. aegyptiaca. Cas9/single guide (sg) RNA constructs were targeted to the second exon of CCD8 in tomato (Solanum lycopersicum L.) plants. Several CCD8Cas9 mutated tomato lines with variable insertions or deletions in CCD8 were obtained with no identified off-targets. Genotype analysis of T1 plants showed that the introduced CCD8 mutations are inherited. Compared to control tomato plants, the CCD8Cas9 mutant had morphological changes that included dwarfing, excessive shoot branching and adventitious root formation. In addition, SL-deficient CCD8Cas9 mutants showed a significant reduction in parasite infestation compared to non-mutated tomato plants. In the CCD8Cas9 mutated lines, orobanchol (SL) content was significantly reduced but total carotenoids level and expression of genes related to carotenoid biosynthesis were increased, as compared to control plants. Taking into account, the impact of plant parasitic weeds on agriculture and difficulty to constitute efficient control methods, the current study offers insights into the development of a new, efficient method that could be combined with various collections of resistant tomato rootstocks

Triptans and CGRP blockade - impact on the cranial vasculature

The trigeminovascular system plays a key role in the pathophysiology of migraine. The activation of the trigeminovascular system causes release of various neurotransmitters and neuropeptides, including serotonin and calcitonin gene-related peptide (CGRP), which modulate pain transmission and vascular tone. Thirty years after discovery of agonists for serotonin 5-HT1B and 5-HT1D receptors (triptans) and less than fifteen after the proof of concept of the gepant class of CGRP receptor antagonists, we are still a long way from understanding their precise site and mode of action in migraine. The effect on cranial vasculature is relevant, because all specific anti-migraine drugs and migraine pharmacological triggers may act in perivascular space. This review reports the effects of triptans and CGRP blocking molecules on cranial vasculature in humans, focusing on their specific relevance to migraine treatment

Community-based post-stroke service provision and challenges: a national survey of managers and inter-disciplinary healthcare staff in Ireland.

ABSTRACT: BACKGROUND: The extent of stroke-related disability typically becomes most apparent after patient discharge to the community. Maximising rehabilitation input at this point can minimise the impact of disability. As part of the Irish National Audit of Stroke Care (INASC), a national survey of community-based allied health professionals and public health nurses was conducted. The aim was to document the challenges to service availability for patients with stroke in the community and to identify priorities for service improvement. METHODS: The study was a cross-sectional tailored interview survey with key managerial and service delivery staff. As comprehensive listings of community-based health professionals involved in stroke care were not available, a cascade approach to information gathering was adopted. Representative regional managers for services incorporating stroke care (N=7) and disciplinary allied health professional and public health nurse managers (N=25) were interviewed (94% response rate). RESULTS: Results indicated a lack of formal, structured community-based services for stroke, with no designated clinical posts for stroke care across disciplines nationally. There was significant regional variation in availability of allied health professionals. Considerable inequity was identified in patient access to stroke services, with greater access, where available, for older patients (\u3e65 years). The absence of a stroke strategy and stroke prevalence statistics were identified as significant impediments to service planning, alongside organisational barriers limiting the recruitment of additional allied health professional staff, and lack of sharing of discipline-specific information on patients. CONCLUSIONS: This study highlighted major gaps in the provision of inter-disciplinary team community-based services for people with stroke in one country. Where services existed, they were generic in nature, rarely inter-disciplinary in function and deficient in input from salient disciplines. Challenges to optimal care included the need for strategic planning; increased funding of healthcare staff; increased team resources and teamwork; and removal of service provision barriers based on age. There were notably many challenges beyond funding. Similar evaluations in other healthcare systems would serve to provide comparative lessons to serve to tackle this underserved aspect of care for patients with stroke and their families

Measuring organisational readiness for patient engagement (MORE) : an international online Delphi consensus study

Date of Acceptance: 28/01/2015. © 2015 Oostendorp et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedWidespread implementation of patient engagement by organisations and clinical teams is not a reality yet. The aim of this study is to develop a measure of organisational readiness for patient engagement designed to monitor and facilitate a healthcare organisation’s willingness and ability to effectively implement patient engagement in healthcarePeer reviewedFinal Published versio