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  1. Low PT, Lai MI, Ngai SC, Abdullah S
    Gene, 2014 Jan 1;533(1):451-5.
    PMID: 24120896 DOI: 10.1016/j.gene.2013.09.075
    Current viral gene delivery vectors for gene therapy are inefficient due to short-lived transgene expression attributed to the cytosine-phosphate-guanine (CpG) motifs in the transgene. Here we assessed the effects of CpG motif reduction in lentiviral (LV) gene delivery context on the level and duration of reporter gene expression in Chinese Hamster Ovary (CHO) cells, Human Immortalized Myelogenous Leukemia (K562) cells and hematopoietic stem cells (HSCs). The cells were transduced with LV carrying Zero-CpG green fluorescent protein (ZGFP) reporter gene, LV/CMV/ZGFP. The GFP expression was compared to its non CpG-depleted GFP reporter gene LV (LV/CMV/GFP) counterpart. The LV/CMV/ZGFP exhibited prolonged transgene expression in CHO cells and HSCs up to 10 days and 14 days, in the respective cells. This effect was not seen in the transduced K562 cells, which may be due to the DNA hypomethylation status of the cancer cell line. Transgene copy number analysis verified that the GFP expression was not from pseudo-transduction and the transgene remained in the genome of the cells throughout the period of the study. The modest positive effects from the LV/CMV/ZGFP suggest that the reduction of CpG in the LV construct was not substantial to generate higher and more prolonged transgene expression.
  2. Low PT, Ng CG, Kadir MS, Tang SL
    Med J Malaysia, 2021 09;76(5):617-623.
    PMID: 34508365
    INTRODUCTION: Non-attendance and medication adherence are longstanding concerns in psychiatric outpatient settings. This study aimed to determine effectiveness of reminders using mobile messaging applications (messaging apps) in improving outpatient attendance and medication adherence among patients with depression.

    METHODS: This was a parallel, open-label randomised controlled trial with participants recruited from psychiatric outpatient services of a teaching hospital in Kuala Lumpur and a secondary hospital in Melaka. Adults (≥18 years) diagnosed with major depressive disorder; capable of reading and understanding English or Bahasa Malaysia; prescribed with at least one antidepressant and owns a smart phone were subsequently randomly assigned (1:1) to receive treatment reminders (intervention) or standard treatment without reminders (control), using a computergenerated randomisation programme. The intervention group received two reminder categories: Outpatient appointment reminders (a day before appointment); and medication reminders (weekly basis). Participants were followed-up over two months. We utilised Montgomery- Asberg Depression Rating Scale (MADRS) to measure the severity of depression; and Brief Adherence Rating Scale (BARS) to assess medication adherence. Primary outcomes were outpatient attendance rates and medication adherence assessed at two months. Secondary outcomes included changes in depression severity within each group at two months; comparison of changes in depression severity between both groups; preferences of participants towards treatment reminders, and reasons for non-attendance among participants. This trial was registered with the National Medical Research Registry, NMRR-19-3466-52001.

    RESULTS: Between February and April 2020, 183 participants were randomised to each group, of whom 179 reached study endpoint (91 [98.9%] of 92 in intervention group and 88 [96.7%] of 91 in control group). All recruited participants (n=183) were analysed using intention-to-treat approach. At two months, intervention group has significantly higher outpatient attendance rates (76.8%) than control group (56.4%) (p=0.002), and reported higher medical adherence percentage (mean difference 23.1, [95%CI 0.4, 35.8]; p<0.001). There was also significant difference in the MADRS score change between both groups (mean difference 3.4, [95%CI 0.4, 6.3]; p=0.025). Treatment reminders preferences among participants varied; forgetfulness was the most commonly reported reason (53%) for missing outpatient appointments.

    CONCLUSION: Reminders through mobile messaging applications significantly improved outpatient attendance and medication adherence among patients with depression. Our findings support the use of messaging apps for treatment reminders in psychiatric outpatient settings. However, concerns regarding confidentiality require careful measures to be taken.

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