Medical principles and practice : international journal of the Kuwait University, Health Science Centre
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Castration-resistant prostate cancer (CRPC) progression after androgen deprivation therapy shows upregulated expression of androgen receptor (AR) splice variants, induced epithelial-to-mesenchymal transition phenotypes and enhanced stem cell characteristics, all of which are associated with resistance to enzalutamide. Since there is no curative treatment for CRPC, innovative treatments are urgently needed. In our recent study, we found that resistance to enzalutamide was partly due to deregulated expression of microRNAs such as miR-34a, miR-124, miR-27b, miR-320 and let-7, which play important roles in regulating AR and stem cell marker gene expression that appears to be linked with resistance to enzalutamide. ⋯ The inhibitory effects of BR-DIM on AR and AR target gene such as prostate-specific antigen were also observed in the clinical trial. Our preclinical and clinical studies provide the scientific basis for a 'proof-of-concept' clinical trial in CRPC patients treated with enzalutamide in combination with BR-DIM. This strategy could be expanded in future clinical trials in patients with PCa to determine whether or not they could achieve a better treatment outcome which could be partly mediated by delaying or preventing the development of CRPC.
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The experience of chronic pain is universal, yet pain management services delivered by health professionals vary substantially, depending on the context and patient. This review is a part of a series that has examined the issue of chronic non-cancer pain services and management in different global cities. The review is structured as a case study of the availability of management services for people living with chronic non-cancer pain within the context of the Kuwaiti health systems, and the cases are built from evidence in the published literature identified through a comprehensive review process. ⋯ This review also includes a description of chronic pain patient personas to highlight expected barriers as well as compliance issues with services likely to be encountered in Kuwait. The case study analysis and persona descriptions illustrate a need to move beyond pain symptom management towards considering the entire person and his/her individual experience of pain such that health care success is judged by enhancement of patient well-being rather than access to services. A road map for improving integrative chronic pain management in Kuwait is discussed.
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Review
Overcoming Resistance to Endocrine Therapy in Breast Cancer: New Approaches to a Nagging Problem.
In the majority of women, breast cancer progresses through increased transcriptional activity due to over-expressed oestrogen receptors (ER). Therapeutic strategies include: (i) reduction of circulating ovarian oestrogens or of peripherally produced oestrogen (in postmenopausal women) with aromatase inhibitors and (ii) application of selective ER modulators for receptor blockade. The success of these interventions is limited by the variable but persistent onset of acquired resistance and by an intrinsic refractiveness which manifests despite adequate levels of ER in about 50% of patients with advanced metastatic disease. ⋯ Multiple mechanisms contributing to therapeutic failure have been proposed: (i) loss or modification of ER expression including epigenetic mechanisms, (ii) agonistic actions of selective ER modulators that may be enhanced through an increased expression of co-activators, (iii) attenuation of the tamoxifen metabolism through expression of genetic variants of P450 cytochromes which leads to more or less active metabolites and (iv) increased growth factor signalling particularly through epidermal growth factor receptor activation of pathways involving keratinocyte growth factor, platelet-derived growth factor, and nuclear factor x03BA;B. In addition, the small non-coding microRNAs, recently recognized as critical gene regulators, exhibit differential expression in tamoxifen-sensitive versus resistant cell lines. Several studies suggest the potential of using these either as targets or as therapeutic agents to modulate EMT regulators as a means of reversing the aggressive metastatic phenotype by reversal of the EMT, with the added benefit of re-sensitization to anti-oestrogens.
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To investigate patients' satisfaction with nursing care by measuring the gap between patients' expectations of care and perceptions of the actual care provided and to identify the areas of nursing care that need improvement. ⋯ Our study showed negative gaps for the 5 nursing service quality dimensions evaluated. This could provide nurses with information about the aspects of nursing care that promote more positive patient outcomes and satisfaction.
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Comparative Study
A Comparative Study of Oral Health Parameters in Molar Incisor Hypomineralization and High-Caries-Risk Children Aged 8-11 Years.
To compare oral health parameters: decayed missing filled teeth (dmft, DMFT), gingival index and plaque index in high-caries-risk children and children with molar incisor hypomineralization (MIH). ⋯ The children in the MIH group had higher DMFT than those without MIH. Hence, the presence of MIH could have a detrimental effect on oral health parameters, especially on DMFT values.