The relationship between strong-ties weak-ties rationality and COVID-19 public stigma: A cross-cultural study of Malaysia and Australia.

We investigated the relationship between strong-ties versus weak-ties rationality and public stigma (PS) during the COVID-19 pandemic. We also explored the cultural group differences (Malaysians vs. Australians) in this relationship. An online survey was conducted in 2021 with a final sample of 830 eligible Malaysians and 394 eligible Australians. Participants completed the multidimensional strong-ties weak-ties rationality Scale (STWTRS) and an adapted public stigma (PS) scale towards COVID-19 patients. Through multiple regression analysis, we found that the strong-ties rationality, ST-Authoritarian rationality, was positively associated with PS-Blame in both countries. However, the variable Country moderated the relationship between ST-Communal and PS-Rejection, with a negative association found in Malaysia and a positive association in Australia. The findings confirmed the strong-ties weak-ties rationality framework, where ST rationality, especially ST-Authoritarian, could explain the cognitive mechanism behind negative attitudes towards those who pose threat towards the in-group survival. However, ST-Communal could buffer the rejection towards the COVID-19 patients in Malaysia due to its emphasis on social harmony. This study can inform future interventions aimed at mitigating stigma and promoting a more inclusive and supportive society in times of crisis.

A qualitative study exploring the epistemology of suffering within a Malaysian Indigenous tribe.

Despite the universal nature of suffering, few studies have examined how Indigenous ethnic minorities in non-western regions understand and respond to adversity. This study explored the epistemology of suffering among the Temiar ethnic group of Peninsular Malaysia using participant observation and semi-structured interviews. Interview transcripts of 43 participants were coded through inductive thematic analysis and a consensual qualitative approach. Three-tier themes were defined and named after subsequent analysis of core ideas and domains in the data. Major adversities reported included a lack of basic needs, lack of land-rights and unjust treatment from authorities, destruction of the forest environment and livelihood, and lack of accessibility and facilities, which were attributed to authorities' negligence of responsibilities, increasing human-animal conflict, environmental threats and imposed lifestyle changes. Faced with adversity, the Temiar endeavoured to survive by working crops and gathering forest resources. They utilized resources from family, fellow villagers, external agencies and spiritual-religious traditions. Theoretical mapping of attribution styles into the Ecological Rationality Framework revealed predominantly external-focused and concrete-perceptual rationalities privileged by strong-ties societies. These findings pointed to the resilience of a strong-ties community while adapting to the systemic suffering and risk factors stemming from a rationality mismatch with modernization and globalization trends. To conclude, we advocate for culture-sensitive mental health and psychiatric practices, as well as sustainable development for the well-being of Indigenous communities locally and globally.

Genetic Ablation of LAT1 Inhibits Growth of Liver Cancer Cells and Downregulates mTORC1 Signaling.

Through a comprehensive analysis of the gene expression and dependency in HCC patients and cell lines, LAT1 was identified as the top amino acid transporter candidate supporting HCC tumorigenesis. To assess the suitability of LAT1 as a HCC therapeutic target, we used CRISPR/Cas9 to knockout (KO) LAT1 in the epithelial HCC cell line, Huh7. Knockout of LAT1 diminished its branched chain amino acid (BCAA) transport activity and significantly reduced cell proliferation in Huh7. Consistent with in vitro studies, LAT1 ablation led to suppression of tumor growth in a xenograft model. To elucidate the mechanism underlying the observed inhibition of cell proliferation upon LAT1 KO, we performed RNA-sequencing analysis and investigated the changes in the mTORC1 signaling pathway. LAT1 ablation resulted in a notable reduction in phosphorylation of p70S6K, a downstream target of mTORC1, as well as its substrate S6RP. This reduced cell proliferation and mTORC1 activity were rescued when LAT1 was overexpressed. These findings imply an essential role of LAT1 for maintenance of tumor cell growth and additional therapeutic angles against liver cancer.

A systematic review on the cultural factors associated with stigma during pandemics.

Both public stigma and perceived self-stigma are prevalent during pandemics threatening a divide among the global community. This systematic review examined the cultural factors associated with viral respiratory-related pandemic stigma. Following PRISMA guidelines, the keywords, "culture, stigma, and pandemic" were searched across relevant databases for empirical papers between January 2000 to March 2022. Quality assessment and coding were adopted in the screening process. Thirty-one articles were included in the final analysis. Themes revealed that collectivistic values, cultural identities, and non-western regions were associated with public (others) stigma; mismatch of cultural values, minority groups, and North America, Asia, Oceania, and African regions were associated with higher perceived and self-stigma. We further mapped the themes into a proposed systemic cultural stigma model to integrate the dynamic intersection of cultural values, identity, and ecology. The cultural factors and their influence on stigma were then explained by drawing on two evolutionary theories: Cultural rationality theory and scapegoating theory. Lastly, we proposed culturally sensitive and responsive practices for stigma management at the community level, especially in non-Western regions during the pandemic recovery phase.

Functional Polymorphisms of the Arachidonic Acid Pathway Associate with Risks and Clinical Outcomes of Allergic Diseases.

INTRODUCTION: The arachidonic acid (AA) pathway plays a crucial role in allergic inflammatory diseases; however, the functional roles of allergy-associated single nucleotide polymorphisms (SNPs) in this pathway remain incompletely illustrated. METHODS: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). We performed population genotyping on n = 2,880 individuals from the SMCSGES cohort to assess the associations of SNPs in the AA pathway genes with asthma and allergic rhinitis (AR). Spirometry assessments were performed to identify associations between SNPs and lung function among n = 74 pediatric asthmatic patients from the same cohort. Allergy-associated SNPs were functionally characterized using in vitro promoter luciferase assay, along with DNA methylome and transcriptome data of n = 237 peripheral blood mononuclear cell (PBMC) samples collected from a subset of the SMCSGES cohort. RESULTS: Genetic association analysis showed 5 tag-SNPs from 4 AA pathway genes were significantly associated with asthma (rs689466 at COX2, rs35744894 at hematopoietic PGD2 synthase (HPGDS), rs11097414 at HPGDS, rs7167 at CRTH2, and rs5758 at TBXA2R, p < 0.05), whereas 3 tag-SNPs from HPGDS (rs35744894, rs11097414, and rs11097411) and 2 tag-SNPs from PTGDR (rs8019916 and rs41312470) were significantly associated with AR (p < 0.05). The asthma-associated rs689466 regulates COX2 promoter activity and associates with COX2 mRNA expression in PBMC. The allergy-associated rs1344612 was significantly associated with poorer lung function, increased risks of asthma and AR, and increased HPGDS promoter activity. The allergy-associated rs8019916 regulates PTGDR promoter activity and DNA methylation levels of cg23022053 and cg18369034 in PBMC. The asthma-associated rs7167 affects CRTH2 expression by regulating the methylation level of cg19192256 in PBMC. CONCLUSIONS: The present study identified multiple allergy-associated SNPs that modulate the transcript expressions of key genes in the AA pathway. The development of a "personalized medicine" approach with consideration of genetic influences on the AA pathway may hopefully result in efficacious strategies to manage and treat allergic diseases.

Assessing the Efficacy of Contextualized Group Counseling Education in Asia: A Mixed Methods Study.

Many experiential learning teaching models are developed in Western cultures, with their efficacy not tested in non-Western cultures, especially in counseling education. This study examined the learning experiences of students (n = 52) enrolled in a culturally contextualized experiential teaching method implemented across a 3-year period in a Malaysian university Masters-level group counseling course. The course changes included group demonstrations by lecturers and peers, live group participation and observation, group dynamics map drawing and debriefing, paired group proposal writing and presentation, and group note- taking. This study adopted a mixed method approach with a short survey consisting of both standardized scales and open-ended questions, administered at the beginning and end of each 12-week semester. Archival data on students' evaluation was also retrieved from the year before the intervention, to compare with the 3 years of intervention. Results showed a statistically significant improvement in students' perceived group leadership skills and leadership characteristics at the end of the course. Students' overall satisfaction with the course quality also improved significantly from the year prior to the implementation of the new teaching method. Qualitative coding identified three major themes-active learning classroom that led to confidence in group counseling knowledge and skills; experiential activities in the tutorial sessions, with opportunities to carry out their proposed group activities; and formative feedback given throughout the semester during tutorial settings contributing to the higher course satisfaction rate. To conclude, we discuss the implications of contextualized experiential learning for higher education counseling pedagogy in the Asian region. Supplementary information: The online version contains supplementary material available at 10.1007/s10447-022-09471-3.

Religiousness and Quality of Life Among Older Adults of Different Ethnic Groups in Malaysia: A Five-Year Follow-up Study.

Research has shown that religion is associated with a better quality of life (QoL). This study aims to examine ethnic differences in the association between religion and the QoL of older adults in a predominantly Muslim population within a multicultural setting. Two-wave data of 3,810 participants consisting of mostly Muslims and older adults aged ≥ 55 years were collected as part of the community health surveys conducted in 2013 and 2018 in the South East Asia Community Observatory (SEACO). Both cross-sectional analyses of baseline data and prospective analyses of longitudinal data were conducted. The associations between religiosity and quality of life were mainly positive in the cross-sectional analysis. In the two-wave analysis, religious importance was negatively associated with QoL among the Malays (B = - 1.103, SE B = 0.029, p < .001) and the Chinese (B = - 0.160, SE B = 0.043, p < .001), and a belief in a higher power control was associated with better QoL among the Malays (B = 0.051, SE B = 0.022, p < .005) and poorer QoL domains among the Indians (physical health: B = - 5.412, SE B = 1.382, p < .001; psychological: B = - 3.325, SE B = 1.42, p < .001; social relationship: B = - 5.548, SE B = 1.616, p < .001; environment: B = - 2.586, SE B = 1.288; p < .05). Our study's mixed results suggest that religiosity is positively associated with quality of life in cross-sectional analyses. However, in longitudinal analyses, the results are different. Conclusions with regard to causality based on cross-sectional analyses may be misleading. Health promotion programs should continue to examine the effect of religiousness on health outcomes over time among aging populations across different ethnic groups.

Risk and Protective Factors for the Mental Wellbeing of Deployed Healthcare Workers During the COVID-19 Pandemic in China: A Qualitative Study.

Background: Though many literatures documented burnout and occupational hazard among healthcare workers and frontliners during pandemic, not many adopted a systemic approach to look at the resilience among this population. Another under-studied population was the large numbers of global healthcare workers who have been deployed to tackle the crisis of COVID-19 pandemic in the less resourceful regions. We investigated both the mental wellbeing risk and protective factors of a deployed healthcare workers (DHWs) team in Wuhan, the epicenter of the virus outbreak during 2020. Method: A consensual qualitative research approach was adopted with 25 DHWs from H province through semi-structured interviews after 3 months of deployment period. Results: Inductive-Deductive thematic coding with self-reflexivity revealed multi-layered risk and protective factors for DHWs at the COVID-19 frontline. Intensive working schedule and high-risk environment, compounded by unfamiliar work setting and colleagues; local culture adaptation; isolation from usual social circle, strained the DHWs. Meanwhile, reciprocal relationships and "familial relatedness" with patients and colleagues; organizational support to the DHWs and their immediate families back home, formed crucial wellbeing resources in sustaining the DHWs. The dynamic and dialectical relationships between risk and protective factors embedded in multiple layers of relational contexts could be mapped into a socio-ecological framework. Conclusion: Our multidisciplinary study highlights the unique social connectedness between patient-DHWs; within DHWs team; between deploying hospital and DHWs; and between DHWs and the local partners. We recommend five organizational strategies as mental health promotion and capacity building for DHWs to build a resilient network and prevent burnout at the disaster frontline.

Periodontal furcation lesions: A survey of diagnosis and management by general dental practitioners.

AIM: The aim of this study was to explore general dental practitioners' (GDPs) attitude to periodontal furcation involvement (FI). MATERIALS AND METHODS: An online survey focused on diagnosis and management of periodontal FI was circulated to GDPs in seven different countries. RESULTS: A total of 400 responses were collected. Nearly a fifth of participants reported rarely or never taking 6-point pocket charts; 65.8% of participants had access to a Nabers probe in their practice. When shown clinical pictures and radiographs of FI-involved molars, the majority of participants correctly diagnosed it. Although 47.1% of participants were very/extremely confident in detecting FI, only 8.9% felt very/extremely confident at treating it. Differences in responses were detected according to country and year of qualification, with a trend towards less interest in periodontal diagnosis and treatment in younger generations. Lack of knowledge of management/referral pathways (reported by 22.8%) and lack of correct equipment were considered the biggest barriers to FI management. Most participants (80.9%) were interested in learning more about FI, ideally face to face followed by online tutorials. CONCLUSIONS: Plans should be put in place to improve general dentists' knowledge and ability to manage FI, as this can have a significant impact on public health.

Cultural Responses to Covid-19 Pandemic: Religions, Illness Perception, and Perceived Stress.

Many psychological researchers have proven the deteriorating effects of the coronavirus disease 2019 (Covid-19) pandemic on public mental health. In Malaysia, various Covid-19 clusters were associated with religious gatherings. From a cultural psychology perspective, how ethno-religious groups respond to this crisis originating from their unique rationality and ecological systems. Therefore, this study aimed to explore the illness perceptions of major religious groups (Christian, Muslim, and Buddhist) in Malaysia toward the Covid-19 pandemic, their stress levels, and the relationship between illness perception, stress, and forms of religious expression during the lockdown period. Through an online survey method, 608 Malaysian religious believers were included in this mixed-method empirical study, which adapted standardized instruments [Duke University Religion Index (DUREL), Brief Illness Perception Questionnaire (BIPQ), and Perceived Stress Scale (PSS)]. Statistical analysis showed that all three groups reported moderate levels of stress in average without any significant difference after controlling for age. Both internal and external forms of religious expression had a significant negative relationship with stress levels. Personal control, comprehension, and emotions domains of illness perception accounted for a significant variance in the stress level. Furthermore, religious expression significantly moderated the relationship between some illness perception domains and stress. Qualitative coding revealed that most participants perceived human behavior and attitudes, sociopolitical, and sociological factors as causal factors to the current pandemic. These findings confirmed the relationship between religious expression, illness belief, and stress regulation during the pandemic lockdown. Incidental findings of age as a potential protective factor for Malaysian believers warrants further study. In the conclusion, implications for public health policymakers and religious communities on pandemic prevention and well-being promotion were discussed.

Factors Associated with Intention to Donate Hematopoietic Stem Cells among Blood Donors.

INTRODUCTION: Past studies pay little attention to the intention to donate hematopoietic stem cells (HSC) among blood donors. This study investigated the level of and the influence of socio-demographic characteristics, knowledge, attitude, subjective norm and self-efficacy on the intention to donate HSC among blood donors. METHODS: This cross-sectional study recruited blood donors at selected public hospitals in the Malaysian State of Sarawak in 2019. A structured questionnaire was developed based on the review of relevant literature. It gathered information on socio-demographic characteristics, knowledge, attitude, subjective norm and self-efficacy on the intention to donate HSC. Variables with a p value <0.200 in bivariate analysis were included in the variable selection for regression modeling to examine their associations with the intention to donate HSC. RESULTS: A total of 569 blood donors participated (94.5% response rate). Overall, 87.1% reported a positive intention to donate HSC. In the regression model, the factor with the greatest association with intention to donate HSC was subjective norms about HSC donation (ß = 0.35, 95% CI 0.27-0.42), followed by attitude about regulations of HSC donation (ß= 0.21, 95% CI 0.13-0.35), self-efficacy on HSC donation (ß = 0.15, 95% CI 0.09-0.32), attitude about the potential side effects of HSC donation (ß = 0.14, 95% CI 0.02-0.10) and highest education level (ß = 0.10, 95% CI 0.03-0.44). CONCLUSIONS: The findings can be used to formulate a better strategy in promoting HSC donation among blood donors in the region.

Pt/Ag Solid Solution Alloy Nanoparticles in Miscibility Gaps Synthesized by Cosputtering onto Liquid Polymers.

Pt/Ag solid solution alloy nanoparticles (NPs) with mean size below 3 nm were obtained with composition in miscibility gaps by cosputtering onto liquid polyethylene glycol (PEG, MW = 600). Adjusting the sputtering currents from 10 to 50 mA did not influence the particle sizes obviously but caused a substantial difference in the composition and distributions of Pt/Ag NPs. This is different from sputtered Pt/Au NPs where particle size is correlated with composition. For a pair of sputtering currents, the formed Pt/Ag alloy NPs have a range of compositions. The normal distribution with Pt of 60.2 ± 16.2 at % is observed for the Pt/Ag sample with a nominal Pt content of 55.9 at %, whereas Pt-rich (85.1 ± 14.0 at % Pt) and Ag-rich (19.8 ± 12.2 at % Pt) Pt/Ag samples with nominal Pt contents of 90.9 and 11.9 at % contain more pure Pt and pure Ag NPs, respectively. Different from NPs obtained in PEG, the sputtered NPs on TEM grids had more uniform composition for a longer sputtering time along with a significant increase of particle sizes. This reveals that PEG hindered the combination of NPs and clusters, resulting in small particle sizes even for long time sputtering and broader composition distributions. Thus, the samples obtained in PEG have the compositions mainly determined by the random atom combination in the vacuum chamber and possibly in initial landing of atom/clusters on the PEG surface.

Effectiveness of a pharmacist-led structured group-based intervention in improving medication adherence and glycaemic control among type 2 diabetes mellitus patients: A randomized controlled trial.

BACKGROUND: A pharmacist-led structured group-based intervention (MEDIHEALTH) was formulated to improve medication adherence among Malay type 2 diabetes mellitus (T2DM) patients in the Malaysian state of Sarawak. OBJECTIVES: The objective of this study was to examine the effectiveness of MEDIHEALTH and its mechanism of impact for improving medication adherence and the glycated haemoglobin (HbA1c) level. METHODS: A two group and parallel randomised controlled trial with a twelve months follow-up period was conducted at two primary health clinics in Malaysia that were surrounded by Malay communities. Malay T2DM patients whose HbA1c was >7% and total score on the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) was <26 were recruited and parallelly randomised to the MEDIHEALTH or usual care (control) groups. The extended theory of planned behaviour was employed to test the mechanism of impact. Repeated measure analysis of variance was used to assess the difference in the estimated marginal mean of the SEAMS scores and HbA1c level between the intervention and control groups at different times. RESULTS: A total of 142 participants were recruited and randomised; three from the intervention group and eight from the control group withdrew before receiving any treatment. Hence, 68 participants in the intervention group and 63 in the control group were included for analyses. The MEDIHEALTH group had a significantly greater increase in the SEAMS score compared to the control group (p < 0.001) at one, three, six and twelve months post-intervention. There was also a significantly greater reduction in HbA1c in the MEDIHEALTH compared to the control group at one, three, six and twelve months post-intervention (p < 0.001). These improvements were mediated by enhancements in perceived behavioural control and knowledge about medications. CONCLUSIONS: The MEDIHEALTH may improve medication adherence and glycaemic control among Malay T2DM patients.

Religion and mental health among older adults: ethnic differences in Malaysia.

OBJECTIVES: Religion and spirituality gain importance as a person ages. Research has shown that religion has a salutary effect on mental health, and it is associated with health differently across ethnic groups. The current study examined ethnic differences in the association between religion and mental health among older adults in a predominantly Muslim population and multicultural setting. METHODS: Data of 7068 participants (4418 Malays, 2080 Chinese and 570 Indians) aged ≥55 years that were collected as part of the community health survey conducted in 2013 in the South East Asia Community Observatory (SEACO) were analyzed using bivariate and multiple regressions. Analyses were stratified by ethnicity. RESULTS: The importance of having an enriched religious/spiritual life was associated with higher scores of depression, anxiety and stress among Chinese and higher score of depression among Malays, while belief in a higher power was associated with better mental health among Malays, Chinese and Indians. CONCLUSION: The current study showed that there were ethnic variations in the associations between religion and mental health, and the associations depended on the religious variable included in the analysis. The findings of this study showed that religion could be another potential channel to improve mental health among older adults by accommodating and understanding their religious beliefs.

Synthesis of Au@Cu2O Core-Shell Nanoparticles with Tunable Shell Thickness and Their Degradation Mechanism in Aqueous Solutions.

Metal@semiconductor core-shell nanoparticles (NPs) are widely used in photocatalysts, sensors, and optical applications owing to their unique metal-semiconductor interface and the integration of the properties from both core and shell materials. Although many efforts have been made toward the precise synthesis of Au@Cu2O core-shell structures, the chemical stability of Au@Cu2O aqueous suspensions, which is of great significance in many related applications, is not mentioned in any published research. Herein we report the synthesis of Au@Cu2O core-shell NPs with small shell thickness from 2 to 40 nm through a wet-chemistry method. The UV-vis absorption properties are found to be tunable with Cu2O thickness in the range of 2-40 nm. Furthermore, the chemical stability of Au@Cu2O core-shell nanoparticle suspensions in water/ethanol mixed solvents is investigated. It is found that water/ethanol mixed solvents with a larger amount of water are more likely to deteriorate the stability of Au@Cu2O NPs by oxidizing Cu2O to CuO. The results from this work may provide useful information for the preparation of metal@Cu2O water-based suspensions that are expected to be used for SERS, photocatalyst, or photothermal applications.

Highly Correlated Size and Composition of Pt/Au Alloy Nanoparticles via Magnetron Sputtering onto Liquid.

Pt/Au alloy nanoparticles (NPs) in a wide composition range have been synthesized by room-temperature simultaneous sputter deposition from two independent magnetron sources onto liquid PEG (MW = 600). The prepared NPs were alloyed with the face-centered cubic (fcc) structure. In addition, the particle sizes, composition, and shape are strongly correlated but can be tailored by an appropriate variation of the sputtering parameters. No individual particle but large agglomerates with partial alloy structure formed at Pt content of less than 16 atom %. Highly dispersed NPs with no agglomeration were observed in PEG when the quantity of Pt is more than 26 atom %. On the other hand, a small amount of Pt could terminate the agglomeration of Au when sputtering on the grids for transmission electron microscope observation. Our experiment and computer simulation carried out by two different methods indicate that the composition-dependent particle size of Pt/Au can be explained by the atomic concentration, formation energy of the cluster, and interaction between different metal atoms and the PEG molecule.

Correction to: Effectiveness and sustainability of a structured group-based educational program (MEDIHEALTH) in improving medication adherence among Malay patients with underlying type 2 diabetes mellitus in Sarawak State of Malaysia: study protocol of a randomized controlled trial.

After publication of the original article [1], the authors have notified us that there are changes to the primary outcome of the study, instrument, subject's inclusion criteria, the funding and acknowledgements. These changes were made during the recruitment of participants and after approved by the Medical Research and Ethics Committee (MREC), National Institutes of Health Malaysia, on 16th November 2018.

Pilot study on functional performance and acceptability of two new synthetic adhesive male condoms (Wondaleaf): a randomized cross-over trial.

OBJECTIVES: This study compared the condom failure rate, safety and acceptability of two new synthetic adhesive male condoms, Wondaleaf-Cap® (WLC) and Wondaleaf-On-Man® (WLM), with a marketed latex external condom Durex®-Together (DT). STUDY DESIGN: We enrolled healthy married, monogamous, heterosexual condom users in a randomized controlled, cross-over, pilot trial in Malaysia. We randomized participants to six groups with different condom use-orders of the experimental WLC and WLM and control latex condom for four episodes for vaginal sex over 1 month for each condom type. We summarized the clinical and non-clinical failure rate, safety and acceptability of each condom type using descriptive statistics. We tested differences in condom failure and acceptability using generalized estimating equations and repeated measure ANOVA respectively. RESULTS: We screened 75 couples and randomized 50 eligible couples. Two couples withdrew before receiving any condom. The remaining used 576 condoms with 192 uses for each condom variant. Clinical failure rates of WLC, WLM and DT were 1.04%, 0% and 0.52%, respectively. Non-clinical failure rates of WLC, WLM and DT were 2.08%, 3.12% and 1.04%, respectively. Removal was found more painful with Wondaleaf products than the DT. Preferences of participants for WLC, WLM and DT were 33.3%, 29.2% and 25%, respectively. Overall, WLC and DT had greater acceptances among male participants than WLM. CONCLUSION: Results of this pilot study support that use of synthetic adhesive male condoms is associated with failure rates similar to those seen with existing latex, and with greater acceptability. A larger study to ascertain non-inferiority is underway. IMPLICATIONS: The availability of synthetic adhesive male condoms may increase the acceptability of condom use. However, removal pain and clinical performance requires further study.

New Water-Soluble Copper(II) Complexes with Morpholine-Thiosemicarbazone Hybrids: Insights into the Anticancer and Antibacterial Mode of Action.

Six morpholine-(iso)thiosemicarbazone hybrids HL1-HL6 and their Cu(II) complexes with good-to-moderate solubility and stability in water were synthesized and characterized. Cu(II) complexes [Cu(L1-6)Cl] (1-6) formed weak dimeric associates in the solid state, which did not remain intact in solution as evidenced by ESI-MS. The lead proligands and Cu(II) complexes displayed higher antiproliferative activity in cancer cells than triapine. In addition, complexes 2-5 were found to specifically inhibit the growth of Gram-positive bacteria Staphylococcus aureus with MIC50 values at 2-5 µg/mL. Insights into the processes controlling intracellular accumulation and mechanism of action were investigated for 2 and 5, including the role of ribonucleotide reductase (RNR) inhibition, endoplasmic reticulum stress induction, and regulation of other cancer signaling pathways. Their ability to moderately inhibit R2 RNR protein in the presence of dithiothreitol is likely related to Fe chelating properties of the proligands liberated upon reduction.

Effectiveness and sustainability of a structured group-based educational program (MEDIHEALTH) in improving medication adherence among Malay patients with underlying type 2 diabetes mellitus in Sarawak State of Malaysia: study protocol of a randomized controlled trial.

BACKGROUND: Amidst the high disease burden, non-adherence to medications among patients with type 2 diabetes mellitus (T2DM) has been reported to be common and devastating. Sarawak Pharmaceutical Services Division has formulated a pharmacist-led, multiple-theoretical-grounding, culturally sensitive and structured group-based program, namely "Know Your Medicine - Take if for Health" (MEDIHEALTH), to improve medication adherence among Malay patients with T2DM. However, to date, little is known about the effectiveness and sustainability of the Program. METHODS/DESIGN: This is a prospective, parallel-design, two-treatment-group randomized controlled trial to evaluate the effectiveness and sustainability of MEDIHEALTH in improving medication adherence. Malay patients who have underlying T2DM, who obtain medication therapy at Petra Jaya Health Clinic and Kota Samarahan Health Clinic, and who have a moderate to low adherence level (8-item Morisky Medication Adherence Scale, Malaysian specific, score <6) were randomly assigned to the treatment group (MEDIHEALTH) or the control group. The primary outcome of this study is medication adherence level at baseline and 1, 3, 6 and 12 months post-intervention. The secondary outcomes are attitude, subjective norms, perceived behavioural control, intention and knowledge related to medication adherence measured at baseline and 1, 6 and 12 months post-intervention. The effectiveness and sustainability of the Program will be triangulated by findings from semi-structured interviews with five selected participants conducted 1 month after the intervention and in-depth interviews with two main facilitators and two managerial officers in charge of the Program 12 months after the intervention. Statistical analyses of quantitative data were conducted using SPSS version 22 and Stata version 14. Thematic analysis for qualitative data were conducted with the assistance of ATLAS.ti 8. DISCUSSION: This study provides evidence on the effectiveness and sustainability of a structured group-based educational program that employs multiple theoretical grounding and a culturally sensitive approach in promoting medication adherence among Malays with underlying T2DM. Both the quantitative and qualitative findings of this study could assist in the future development of the Program. TRIAL REGISTRATION: National Medical Research Register, NMRR-17-925-35875 (IIR). Registered on 19 May 2017. ClinicalTrials.gov, NCT03228706 . Registered on 25 July 2017.