AREA COVERED: The presented review article mainly summarizes the developments of small molecule KRAS inhibitors as drug candidates and rational approaches that are being utilized for the selective targeting of KRAS signaling in the mutant cancer cells.
EXPERT OPINION: After the initial success in targeting the mutant KRAS G12C variants, the search has been shifted to address the challenges concerning the resistance and efficacy of small molecule KRAS inhibitors. However, the contribution of other KRAS mutations at G12V, G13C, and G13D variants causing cancers is much higher than the mutations at G12C. In view of this aspect, specific attention is required to target all other mutations as well. Accordingly, for the development of KRAS targeted therapies, the design of small molecule inhibitors that can inhibit KRAS signaling and as well as target inhibition of other signaling pathways like RAS-SOS and RAS-PI3K has to be explored extensively.
METHODS: This study, involving a series of N-of-1 trials, included 21 participants who had a history of neuropathic plantar forefoot ulcers. Participants were recruited from two public hospitals and one private podiatry clinic in Sydney, New South Wales, Australia. This trial is non-randomised and unblinded. Participants will be recruited from three sites, including two high-risk foot services and a private podiatry clinic in Sydney, Australia. Mobilemat™ and F-Scan® plantar pressure mapping systems by TekScan® (Boston, USA) will be used to measure barefoot and in-shoe plantar pressures. Participants' self-reports will be used to quantify the wearing period over a certain period of between 2 and 4 weeks during the trial. Participant preference toward footwear, insole design and quality-of-life-related information will be collected and analysed. The descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics (version 27). And the software NVivo (version 12) will be utilised for the qualitative data analysis.
DISCUSSION: This is the first trial assessing footwear and insole interventions in people with diabetes by using a series of N-of-1 trials. Reporting self-declared wearing periods and participants' preferences on footwear style and aesthetics are the important approaches for this trial. Patient-centric device designs are the key to therapeutic outcomes, and this study is designed with that strategy in mind.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000699965p. Registered on June 23, 2020.
METHODS: A descriptive cross-sectional study was used to collect information from 502 Nepalese migrant workers in the arrival section of Tribhuvan International Airport from May to June 2019 using purposive sampling. Workers with a minimum work experience of 6 months and above were included in the study. A structured questionnaire with socio-demographic items was used along with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and WHO (five) wellbeing scale for measuring the subjective psychological wellbeing and screening for depression.
RESULTS: The mean age of the respondents was 32.97 years. Majority (41.8%) of the respondents had work experience in Qatar and 63.7% had work experience of 1-5 years. The results suggested that 14.4% had mild to severe depression while 4.4% had a moderate level of anxiety. The WHO5 wellbeing index score suggested that 14.1% of the respondents had a score below 13, which is suggestive of poor psychological wellbeing. Further, the country of work (p = 0.043), sleeping hours (p = 0.001), occupation (p = 0.044), working hours (p = 0.000), water intake (p = 0.010) and anxiety level (p = 0.000) were found to be significantly associated with depression score. Similarly, sleeping hours (p = 0.022), occupation (p = 0.016), working hours (p = 0.000), water intake (p = 0.010), and anxiety level (0.000) were significantly associated with the WHO5 wellbeing score.
CONCLUSIONS: Nepalese migrant workers in the Gulf countries (United Arab Emirates, Saudi Arabia, Qatar, Oman, Kuwait, Bahrain) and Malaysia bear an important burden of psychological morbidities. This highlights the need to prioritize the migrant worker's mental health by Nepal as well as Gulf countries and Malaysia.
AIM OF THE STUDY: To determine the patterns and reasons for kratom use among current and former opioid poly-drug users in Malaysia.
MATERIALS AND METHODS: A total of 204 opioid poly-drug users (142 current users vs. 62 former users) with current kratom use history were enrolled into this cross-sectional study. A validated UPLC-MS/MS method was used to evaluate the alkaloid content of a kratom street sample.
RESULTS: Results from Chi-square analysis showed that there were no significant differences in demographic characteristics between current and former opioid poly-drug users except with respect to marital status. Current users had higher odds of being single (OR: 2.2: 95%CI: 1.21-4.11; p