Derivation of two induced pluripotent stem cell lines from a healthy control subject.

Two human induced pluripotent stem cell lines, LEIi021-A and LEIi021-B, were derived from dermal fibroblasts from a healthy control subject from an Australian Aboriginal family with retinitis pigmentosa-11. Reprogramming was performed using episomal vectors expressing OCT4, SOX2, LIN28, L-MYC, KLF4 and mp53DD. Pluripotency markers were expressed in both LEIi021-A and LEIi021-B lines.

Establishment of an induced pluripotent stem cell line LEIi019-A from an early-onset retinal dystrophy patient with the autosomal dominant OTX2 c.259G>A variant.

The human induced pluripotent stem cell (iPSC) line LEIi019-A was generated from a patient with early-onset pattern dystrophy caused by a heterozygous mutation NM_001270525.1:c.259G>A (p.

Pathogenesis and Treatment of Usher Syndrome Type IIA.

Usher syndrome (USH) is the most common form of deaf-blindness, with an estimated prevalence of 4.4 to 16.6 per 100,000 people worldwide.

Determinants of Disease Penetrance in -Associated Retinopathy.

Retinitis pigmentosa 11 (RP11) is caused by dominant mutations in , however a significant proportion of mutation carriers do not develop retinopathy. Here, we investigated the relationship between polymorphism, repeat copy number and disease penetrance in RP11 patients and non-penetrant carriers (NPCs). We further characterized and expression in fibroblasts from eight RP11 patients and one NPC from a family carrying the c.

Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides.

Antisense oligomers (AOs) are increasingly being used to modulate RNA splicing in live cells, both for research and for the development of therapeutics. While the most common intended effect of these AOs is to induce skipping of whole exons, rare examples are emerging of AOs that induce skipping of only part of an exon, through activation of an internal cryptic splice site. In this report, we examined seven AO-induced cryptic splice sites in six genes.

Generation of two induced pluripotent stem cell lines from a patient with recessive inherited retinal disease caused by compound heterozygous mutations in SNRNP200.

The human induced pluripotent stem cell (iPSC) lines LEIi015-A and LEIi015-B were derived from a patient with inherited retinal disease caused by compound heterozygous mutations in the SNRNP200 gene (c.[1792C>T];[3341T>C]). Dermal fibroblasts were transfected with episomal plasmids carrying transgenes encoding OCT4, SOX2, KLF4, L-MYC, LIN28, mir302/367 microRNA and shRNA for P53.

Generation of three induced pluripotent stem cell lines from a patient with Usher syndrome caused by biallelic c.949C > A and c.1256G > T mutations in the USH2A gene.

Mutations in the USH2A gene are the most common cause of Usher syndrome and autosomal recessive non-syndromic retinitis pigmentosa. Here, we describe the generation of three induced pluripotent stem cell lines from dermal fibroblasts derived from a patient carrying biallelic c.949C > A and c.

Consequences of Making the Inactive Active Through Changes in Antisense Oligonucleotide Chemistries.

Antisense oligonucleotides are short, single-stranded nucleic acid analogues that can interfere with pre-messenger RNA (pre-mRNA) processing and induce excision of a targeted exon from the mature transcript. When developing a panel of antisense oligonucleotides to skip every dystrophin exon, we found great variation in splice switching efficiencies, with some antisense oligonucleotides ineffective, even when directed to canonical splice sites and transfected into cells at high concentrations. In this study, we re-evaluated some of these ineffective antisense oligonucleotide sequences after incorporation of locked nucleic acid residues to increase annealing potential.

Antibiotic knowledge, attitudes and practices: new insights from cross-sectional rural health behaviour surveys in low-income and middle-income South-East Asia.

Introduction: Low-income and middle-income countries (LMICs) are crucial in the global response to antimicrobial resistance (AMR), but diverse health systems, healthcare practices and cultural conceptions of medicine can complicate global education and awareness-raising campaigns. Social research can help understand LMIC contexts but remains under-represented in AMR research.

Objective: To (1) Describe antibiotic-related knowledge, attitudes and practices of the general population in two LMICs.

The 'Drug Bag' method: lessons from anthropological studies of antibiotic use in Africa and South-East Asia.

Understanding the prevalence and types of antibiotics used in a given human and/or animal population is important for informing stewardship strategies. Methods used to capture such data often rely on verbal elicitation of reported use that tend to assume shared medical terminology. Studies have shown the category 'antibiotic' does not translate well linguistically or conceptually, which limits the accuracy of these reports.

How context can impact clinical trials: a multi-country qualitative case study comparison of diagnostic biomarker test interventions.

Background: Context matters for the successful implementation of medical interventions, but its role remains surprisingly understudied. Against the backdrop of antimicrobial resistance, a global health priority, we investigated the introduction of a rapid diagnostic biomarker test (C-reactive protein, or CRP) to guide antibiotic prescriptions in outpatient settings and asked, "Which factors account for cross-country variations in the effectiveness of CRP biomarker test interventions?"

Methods: We conducted a cross-case comparison of CRP point-of-care test trials across Yangon (Myanmar), Chiang Rai (Thailand), and Hanoi (Vietnam). Cross-sectional qualitative data were originally collected as part of each clinical trial to broaden their evidence base and help explain their respective results.

The Consequences of AMR Education and Awareness Raising: Outputs, Outcomes, and Behavioural Impacts of an Antibiotic-Related Educational Activity in Lao PDR.

Education and awareness raising are the primary tools of global health policy to change public behaviour and tackle antimicrobial resistance. Considering the limitations of an awareness agenda, and the lack of social research to inform alternative approaches, our objective was to generate new empirical evidence on the consequences of antibiotic-related awareness raising in a low-income country context. We implemented an educational activity in two Lao villages to share general antibiotic-related messages and also to learn about people's conceptions and health behaviours.

A Comparison of Patients' Local Conceptions of Illness and Medicines in the Context of C-Reactive Protein Biomarker Testing in Chiang Rai and Yangon.

Antibiotic resistance is not solely a medical but also a social problem, influenced partly by patients' treatment-seeking behavior and their conceptions of illness and medicines. Situated within the context of a clinical trial of C-reactive protein (CRP) biomarker testing to reduce antibiotic over-prescription at the primary care level, our study explores and compares the narratives of 58 fever patients in Chiang Rai (Thailand) and Yangon (Myanmar). Our objectives are to 1) compare local conceptions of illness and medicines in relation to health-care seeking and antibiotic demand; and to 2) understand how these conceptions could influence CRP point-of-care testing (POCT) at the primary care level in low- and middle-income country settings.

Antibiotics and activity spaces: protocol of an exploratory study of behaviour, marginalisation and knowledge diffusion.

Background: Antimicrobial resistance (AMR) is a global health priority. Leading UK and global strategy papers to fight AMR recognise its social and behavioural dimensions, but current policy responses to improve the popular use of antimicrobials (eg, antibiotics) are limited to education and awareness-raising campaigns. In response to conceptual, methodological and empirical weaknesses of this approach, we study people's antibiotic-related health behaviour through three research questions.

Catalase restores the altered mRNA expression of collagen and matrix metalloproteinases by dermal fibroblasts exposed to reactive oxygen species.

We investigated the effects of reactive oxygen species (ROS) on mRNA expression of proalpha1(I) collagen, proalpha1(III) collagen, matrix metalloproteinases-1 (MMP-1), 72 kDa type IV collagenase (MMP-2), and tissue inhibitor of metalloproteinase (TIMP-1) by normal human dermal fibroblasts in a novel three-dimensional culture. Fibroblasts exposed to ROS generated by the hypoxanthine-xanthine oxidase system revealed an increased mRNA expression of MMP-1 and MMP-2 with a maximum at 48 h and 72 h after exposure. A slight increase in the mRNA level of tissue inhibitor of metalloproteinase (TIMP-1) was observed.