The Promises and Pitfalls of CRISPR-Mediated Base Editing in Stem Cells.

Stem cells such as induced pluripotent stem cells, embryonic stem cells, and hematopoietic stem and progenitor cells are growing in importance in disease modeling and regenerative medicine. The applications of CRISPR-based gene editing to create a mélange of disease and nondisease stem cell lines have further enhanced the utility of this innately versatile group of cells in the studies of human genetic disorders. Precise base edits can be achieved using a variety of CRISPR-centric approaches, particularly homology-directed repair and the recently developed base editors and prime editors. Despite its much-touted potential, editing single DNA bases is technically challenging. In this review, we discuss the strategies for achieving exact base edits in the creation of various stem cell-based models for use in elucidating disease mechanisms and assessing drug efficacy, and the unique characteristics of stem cells that warrant special considerations.

CRISPR Gene-Editing Models Geared Toward Therapy for Hereditary and Developmental Neurological Disorders.

Hereditary or developmental neurological disorders (HNDs or DNDs) affect the quality of life and contribute to the high mortality rates among neonates. Most HNDs are incurable, and the search for new and effective treatments is hampered by challenges peculiar to the human brain, which is guarded by the near-impervious blood-brain barrier. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), a gene-editing tool repurposed from bacterial defense systems against viruses, has been touted by some as a panacea for genetic diseases. CRISPR has expedited the research into HNDs, enabling the generation of in vitro and in vivo models to simulate the changes in human physiology caused by genetic variation. In this review, we describe the basic principles and workings of CRISPR and the modifications that have been made to broaden its applications. Then, we review important CRISPR-based studies that have opened new doors to the treatment of HNDs such as fragile X syndrome and Down syndrome. We also discuss how CRISPR can be used to generate research models to examine the effects of genetic variation and caffeine therapy on the developing brain. Several drawbacks of CRISPR may preclude its use at the clinics, particularly the vulnerability of neuronal cells to the adverse effect of gene editing, and the inefficiency of CRISPR delivery into the brain. In concluding the review, we offer some suggestions for enhancing the gene-editing efficacy of CRISPR and how it may be morphed into safe and effective therapy for HNDs and other brain disorders.

Community Pharmacists' Knowledge, Attitude, and Practice in Providing Self-Care Recommendations for the Management of Premenstrual Syndrome.

Background and objectives: Premenstrual syndrome (PMS) comprises a variety of physical and emotional symptoms that affect women of reproductive age. The distress caused by PMS often leads to self-medication, and many over-the-counter or non-prescription products are available for relieving PMS symptoms. The choice of a suitable product should be based on advice from a health professional, such as a community pharmacist. Hence, we assessed the knowledge, attitude, and practice of Malaysian community pharmacists in providing self-care recommendations for the management of PMS. Materials and Methods: A cross-sectional survey was carried out in Kuala Lumpur, Malaysia from September to November 2018 using a self-administered questionnaire. The respondents were community pharmacists working in Kuala Lumpur and were chosen from a list of Type A license holders in the city. Results: We achieved a response rate of 79% and included 181 questionnaires in the final analysis. Of the 181 respondents, most of them (76.8%; n = 139) had medium to good levels of knowledge of PMS. Likewise, most of the respondents (78.5%; n = 142) had positive attitudes toward their role in PMS management. Having taken courses on managing minor illnesses in women substantially enhanced their levels of knowledge of (p = 0.002), but not their attitude towards, PMS management. Among the PMS-relieving products, the most commonly recommended products were ibuprofen (79%; n = 143), mefenamic acid (74.5%; n = 135), and naproxen (66.9%; n = 121), which are well known for their anti-inflammatory effect. This suggests that the respondents based their product choice on sound evidence. Conclusions: Community pharmacists can play an important role in the management of PMS. In future work, a larger sample can be assembled to obtain more insight into the readiness of community pharmacists to help women in self-managing PMS and establish a specialized service to this end.