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Background Therapies targeting certain CFTR mutants have been approved, yet variations in clinical response highlight the need for in-vitro and genetic tools that predict patient-specific clinical outcomes. Toward this goal, the CF Canada-Sick Kids Program in Individual CF Therapy (CFIT) is generating a "first of its kind", comprehensive resource containing patient-specific cell cultures and data from 100 CF individuals that will enable modeling of therapeutic responses. Methods The CFIT program is generating: 1) nasal cells from drug naive patients suitable for culture and the study of drug responses in vitro , 2) matched gene expression data obtained by sequencing the RNA from the primary nasal tissue, 3) whole genome sequencing of blood derived DNA from each of the 100 participants, 4) induced pluripotent stem cells (iPSCs) generated from each participant's blood sample, 5) CRISPR-edited isogenic control iPSC lines and 6) prospective clinical data from patients treated with CF modulators. Results To date, we have recruited 57 of 100 individuals to CFIT, most of whom are homozygous for F508del (to assess in-vitro: in-vivo correlations with respect to ORKAMBI response) or heterozygous for F508del and a minimal function mutation. In addition, several donors are homozygous for rare nonsense and missense mutations. Nasal epithelial cell cultures and matched iPSC lines are available for many of these donors. Conclusions This accessible resource will enable development of tools that predict individual outcomes to current and emerging modulators targeting F508del-CFTR and facilitate therapy discovery for rare CF causing mutations.

The combination therapies ORKAMBITM and TRIKAFTATM are approved for people who have the F508del mutation on at least one allele. In this study we examine the effects of potentiator and corrector combinations on the rare mutation c.3700A>G. This mutation produces a cryptic splice site that deletes six amino acids in NBD2 (I1234-R1239del). Like F508del it causes protein misprocessing and reduced chloride channel function. We show that a novel cystic fibrosis transmembrane conductance regulator CFTR modulator triple combination (AC1, corrector, AC2-2, co-potentiator and AP2, potentiator), rescued I1234-R1239del-CFTR activity to WT-CFTR level in HEK293 cells. Moreover, we show that although the response to ORKAMBI was modest in nasal epithelial cells from two individuals homozygous for I1234-R1239del-CFTR, a substantial functional rescue was achieved with the novel triple combination. Interestingly, while both the novel CFTR triple combination and TRIKAFTATM treatment showed functional rescue in gene-edited I1234-R1239del-CFTR-expressing HBE cells and in nasal cells from two CF patients heterozygous for I1234-R1239del/W1282X, nasal cells homozygous for I1234-R1239del-CFTR showed no significant response to the TRIKAFTATM combination. These data suggest a potential benefit of CFTR modulators on the functional rescue of I1234-R1239del -CFTR, which arises from the rare CF-causing mutation c.3700A>G, and highlight that patient tissues are crucial to our full understanding of functional rescue in rare CFTR mutations.

Background: The aim of this study was to develop a “behavioural diagnosis” of factors influencing the uptake of the MIND diet in 40-55-year olds according to the COM-B model, in order to reduce the risk of cognitive decline in later life. Comparing a Mediterranean (Italy) and non-Mediterranean (Northern Ireland) country to inform an intervention. This study also sought to identify intervention functions and behaviour change techniques (BCTs) that are likely to be effective in changing MIND diet behaviour. Methods: This was a qualitative study that was used to elicit beliefs surrounding Capability, Opportunity, Motivation and Behaviour (COM-B) with adhering to a diet associated with a reduced risk of cognitive decline, the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND diet). This study further elaborated the COM-B components into the 14 domains of the Theoretical Domains Framework (TDF) to further understand behaviour. Twenty-five Northern Irish (NI) and Italian participants were recruited onto the study, to take part in either a focus group or an interview. Participants were both male and female aged between 40-55 years. Results: Thematic analysis revealed that the main barriers to the uptake of the MIND diet were; time, work environment (opportunity), taste preference and convenience (motivation). Culture (motivation), seasonal foods and lack of family support (opportunity) to be a barrier to the Italian sample only. The main facilitators reported were; improved health, memory, planning and organisation (motivation) and access to good quality food (opportunity). Cooking skills, knowledge (capability) and heathy work lunch (opportunity) being a facilitator to the Italian sample only. Five intervention functions and fifteen BCTs were identified for possible inclusion in intervention development. Conclusions: The “behavioural diagnosis” provides comparisons and valuable insight into the personal, social and environmental factors that participants report as barriers and facilitators to the uptake of the MIND diet in the two samples. More barriers to healthy dietary change were found than facilitators. There is a need for interventions that increase capability, opportunity and motivation to aid behaviour change. The “behavioural diagnosis” from this study will be used to design a behaviour change intervention using the subsequent steps from the Behaviour Change Wheel (BCW).

Outside of the common law and civil law legal traditions, what is termed “Islamic law” forms one of the world's largest legal systems. There are more than one billion Muslims world-wide, and millions of those Muslims populate some of the world's richest trading zones. As of 2005, the Gulf Cooperation Council (G.C.C.), comprised of Saudi Arabia, Kuwait, Bahrain, Qatar, Oman, and the United Arab Emirates, was the United States' fifth largest trading partner.