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As a direct result of advancements in digital technology and the Internet, the copyright protection and information integrity of multimedia that are being published across the Internet have emerged as a major and urgent issue that needs to be addressed. The technique of digital watermarking may be used to protect intellectual property. In terms of authentication, resilience, storage, and capacity of digital watermarking information, there is still room for development. Blockchain's potential in video copyright protection and management applications has motivated researchers. Copyright owners and consumers may now communicate directly via copyright protection apps built on the blockchain, eliminating the need for distributers and the associated fees. Nonetheless, the current blockchain-based video watermarking solutions require storing a significant number of coordinates depending on the watermark size and are susceptible to video frame attacks on the video frame texture region. This study proposes an enhanced video copyright management approach that incorporates digital watermarking, the blockchain, and a perceptual hash function. Watermark information is stored on a blockchain structure, which also acts as a timestamp for verification purposes. To verify watermark data without the source video, a perceptual hash function is employed to compute a hash value based on the structural information of video frames. The contribution is in learning how to extract a hash function from a small number of video frames that still adequately represent a large amount of video content while also reducing the number of unnecessary video frames and the amount of computation required to summarize and index that content in a blockchain. This expedites the dissemination of copyrighted works and increases their security and readability, hence facilitating their circulation on the Internet. Our experimental results demonstrate that this approach is memory efficient, as it only needs to store one key for each key frame, regardless of the size of the watermark. Additionally, the overall robustness is greatly improved by using the blockchain's random hash function. Therefore, new and important advancements in video watermarking have been realized because of this effort., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Darwish et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immunisation is one of public health's greatest success stories, yet, annually, 20 million children miss out entirely or partially on routine immunisation. National immunisation estimates have the United Arab Emirates (UAE) lagging behind with 4% of children under the age of 1 not having received any vaccines. Vaccine hesitancy is considered one of the biggest barriers to vaccination. This study aims to evaluate the UAE's parents' vaccination attitudes and practices as well as estimate vaccine hesitancy's prevalence and determinants., Methodology: This cross-sectional, descriptive study collected data from parents across the UAE during the months of March and April 2024. The 60-item questionnaire included the Parental Attitudes towards Childhood Vaccines scale (PACV), the Vaccine Hesitancy Scale, and the Digital Vaccine Literacy (DVL) scale. Univariate, bivariate (chi-squared test), and multivariate (logistic regression) analyses were conducted., Results: A total of 550 responses were retained. 84.55% of participants were female (n = 465/550), half were middle-aged (31-45 years old), and 21.09% (n = 116/550) were healthcare workers. 94.36% (n = 519/550) had their child/children receive all mandated vaccines. Only 39.82% (n = 219/550) found their level of knowledge about childhood vaccinations to be good/excellent. 70.11% (n = 386/550) of participants had high digital vaccine literacy. More than 95% had positive attitudes towards measles, meningitis, and pertussis vaccines. 14.00% (n = 77/550) were identified as vaccine-hesitant according to the PACV. Overall, using general practitioner/ paediatrician as a knowledge source, digital vaccine literacy, perceived children's vaccine knowledge, and nationality were associated with lower vaccine hesitancy status., Conclusion: Vaccine hesitancy exists and is prevalent in the UAE; however, the majority of participants reported high trust in vaccines, the local healthcare systems and physicians. Vaccine hesitancy can be tackled but will require tailored solutions and proactive healthcare workers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Barqawi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immune checkpoint inhibitors (ICIs) have emerged as an effective treatment for colorectal cancer (CRC). Studies indicate that the composition of gut microbiota could potentially serve as a biomarker for predicting the clinical effectiveness of immune checkpoint inhibitors., Methods: Following PRISMA guidelines, the review was conducted after registering the protocol with PROSPERO. A comprehensive literature search was carried out across five databases: PubMed, Scopus, Web of Science, Embase, and Cochrane Library. Assessment tools from the National Institutes of Health (NIH) were used to gauge the quality of the studies., Results: A total of 5,132 papers were identified, and three studies and one conference abstract published between 2017-2022 met the inclusion criteria and were summarized in a descriptive synthesis table. These four studies were in accord with the following findings, four main phyla, Firmicutes, Bacteroidata, Actinobacteria, and Verrucomicrobiota were associated with CRC patients' clinical response toward ICIs treatment. Ruminococcaceae was predominantly related to CRC patients responding to therapy, while the Micrococcaceae family was more common among the non-responders. Bacterial taxa such as Faecalibacterium and Prevotellaceae were associated with better responses to ICIs and could be predictive biomarkers. The signature of fecal microbiota with Akkermansia muciniphila and Eubacterium rectale enrichment, and Rothia mucilaginosa depletion could independently predict better response to ICIs in patients with CRC., Conclusion: The findings have brought attention to the notable differences in terms of richness and composition of microbiota between patients who responded positively to the treatment and those who did not. Bacterial species and families, such as Faecalibacterium, Bifidobacterium, Lachnospiraceae, Akkermansia sp., Ruminococcaceae, and Prevotellaceae, have consistently surfaced as potential indicators of immunotherapeutic responses. Furthermore, this review also emphasizes the need for additional comprehensive, multi-center studies with larger sample sizes to validate reported microbiota and expand our understanding of the role of gut microbiota in CRC ICIs therapy. PROSPERO ID: CRD42021277691., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ajab et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Academic achievement is crucial for the social and economic development of young people and determines the quality of education of a nation. According to different studies, food insecurity adversely affects children's health, nutrition, and subsequent decline in academic performance by impairing students' ability to learn and therefore affects the achievement of the Sustainable Development Goals (SDGs) of quality education and lifelong learning opportunities for all. To provide evidence on the association of food insecurity with academic performance is necessary. The current study assessed household food insecurity and its association with academic performance among primary school adolescents in Hargeisa City, Somaliland., Methods: A school-based cross-sectional study was conducted among 630 primary school adolescents from December 2021 to March 2022. Students were selected using a multistage sampling technique. An interviewer-administered questionnaire was used to collect data on household food security and socio-demographic variables and entered into Epi data version 3.1. The data was exported to SPSS version 26 for descriptive and multivariable logistic regression analysis. Odds ratios and their 95% confidence intervals together with p <0.05 were utilized to declare statistical significance., Results: The prevalence of food insecurity among school adolescents was 59.21%. The majority (55.40%) of the school adolescents were poor academic performers. The frequency of adolescents' poor academic performance was significantly high (71.05%) among food insecure households (P < 0.001) as compared to their counterparts whose households were food secure (32.68%). On multivariable analysis, household food insecurity (AOR = 5.24, 95%CI = 3.17-8.65), school absenteeism (AOR = 3.49, 95%CI = 2.20-5.53), spending >2h/day watching TV / screen media use (AOR = 9.08, 95%CI = 4.81-17.13), high and middle wealth households (AOR = 0.51, 95%CI = 0.30-0.88) (AOR = 0.40, 95%CI = 0.21-0.76) and habitual breakfast consumption (AOR = 0.08, 95%CI = 0.03-0.20) had shown statistically significant association with academic performance among primary school adolescents., Conclusion: The present study revealed that household food insecurity has a high association with adolescents' academic performance. The prevalence of food insecurity is moderate, based on the household food insecurity access scale. The results indicate the need for policies and programs intended to improve household income by developing income-generation programs for lower-income families and enhance feeding programs such as national school lunch and school feeding across schools in the country., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Adam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Industry 4.0, the adoption of new technology has played a major role in the transportation sector, especially in the electric vehicles (EVs) domain. Nevertheless, consumer attitudes towards EVs have been difficult to gauge but researchers have tried to solve this puzzle. The prior literature indicates that individual attitudes and technology factors are vital to understanding users' adoption of EVs. Thus, the main aim is to meticulously investigate the unexplored realm of EV adoption within nations traditionally reliant on oil, exemplified by Saudia Arabia. By integrating the "task technology fit" (TTF) model and the "unified theory of acceptance and usage of technology" (UTAUT), this research develops and empirically validates the framework. A cross-section survey approach is adopted to collect 273 valid questionnaires from customers through convincing sampling. The empirical findings confirm that the integration of TTF and UTAUT positively promotes users' adoption of EVs. Surprisingly, the direct effect of TTF on behavioral intentions is insignificant, but UTAUT constructs play a significant role in establishing a significant relationship. Moreover, the UTAUT social influence factor has no impact on the EVs adoption. This groundbreaking research offers a comprehensive and holistic methodology for unravelling the complexities of EV adoption, achieved through the harmonious integration of two well-regarded theoretical frameworks. The nascent of this research lies in the skilful blending of technological and behavioral factors in the transportation sector., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alwadain et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: When the COVID-19 pandemic was declared, Yemen, a country facing years of conflict had only one laboratory with PCR testing capacity. In this article, we describe the outcome of the implementation of molecular based diagnostics platform in Yemen and highlight the key milestones the country went through to increase access to testing for its populations residing in a geographically vast and politically divided country., Methods: A retrospective assessment of COVID-19 laboratory response activities was done detailing the needs assessment process, timelines, geographical coverage, and outcomes of the activities. Laboratory data was analyzed to construct the geographical locations of COVID-19 testing laboratories and the numbers of tests performed in each facility to highlight the demands of testing for travelers. Finally, we discuss the impact these activities had in enabling the movement of people across international borders for economic gains and in delivery of critical humanitarian aid., Outcome: PCR testing capacities in Yemen significantly improved, from one laboratory in Sanaa in April 2020 to 18 facilities across the country by June 2022. In addition, the number of functional Real-Time PCR thermocyclers increased from one to 32, the PCR tests output per day improved from 192 to 6144 tests per day. Results from analysis of laboratory data showed there were four peaks of COVID-19 in Yemen as October 2022. The majority of laboratory tests were performed for travelers than for medical or public health reasons. Demand for laboratory testing in Yemen was generally low and waned over time as the perceived risk of COVID-19 declined, in parallel with rollout of the COVID-19 vaccines., Discussion/conclusion: The successful expansion of laboratory testing capacity was instrumental in the control and management of COVID-19 cases and critical in the implementation of public response strategies, including restrictions on gathering. Laboratory testing also facilitated the movement of humanitarian agencies and delivery of aid and enabled hundreds of thousands of Yemeni nationals to travel internationally. By virtue of these outcomes, the impact of laboratory strengthening activities was thus felt in the health sector and beyond., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bashir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Influenza is a contagious respiratory illness that can cause life-threatening complications among high-risk groups. Estimating the economic burden of influenza is essential to guide policy-making on influenza vaccination programmes, especially in resource-limited settings. This study aimed to estimate the economic burden of influenza on older adults (those aged ≥60 years) in Malaysia from the provider's perspective., Methods: The main data source in this study was the MY-DRG Casemix database of a teaching hospital in Malaysia. Cases with principal and secondary diagnoses coded in the International Classification of Diseases version 10 (ICD-10) as J09, J10.0, J10.1, J10.8, J11.0, J11.1, J11.8, J12.8, and J12.9, which represent influenza and its complications, were included in the study. The direct cost of influenza at all severity levels was calculated from the casemix data and guided by a clinical pathway developed by experts. The effect of the variations in costs and incidence rate of influenza for both the casemix and clinical pathway costing approaches was assessed with sensitivity analysis., Results: A total of 1,599 inpatient and 407 outpatient influenza cases were identified from the MY-DRG Casemix database. Most hospitalised cases were aged <18 years (90.6%), while 77 cases (4.8%) involved older people. Mild, moderate, and severe cases comprised 56.5%, 35.1%, and 8.4% of cases, respectively. The estimated average annual direct costs for managing mild, moderate, and severe influenza were RM2,435 (USD579), RM6,504 (USD1,549), and RM13,282 (USD3,163), respectively. The estimated total annual economic burden of influenza on older adults in Malaysia was RM3.28 billion (USD782 million), which was equivalent to 10.7% of the Ministry of Health Malaysia budget for 2020. The sensitivity analysis indicated that the influenza incidence rate and cost of managing severe influenza were the most important factors influencing the total economic burden., Conclusions: Overall, our results demonstrated that influenza imposes a substantial economic burden on the older Malaysian population. The high cost of influenza suggested that further efforts are required to implement a preventive programme, such as immunisation for older people, to reduce the disease and economic burdens., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mad Tahir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This is cross-sectional research done to assess the readiness of the private Malaysian general practitioners (GPs) for the implementation of the national health financing scheme. The study focused on their levels of knowledge and attitudes towards the types of health financing scheme, gatekeeper roles in the health financing scheme, and their participation in the PeKa B40 scheme. Their acceptance and level of participation in the national health financing scheme (NHFS) were also assessed. A set of self-designed and pre-tested questionnaires focusing on the aforementioned objectives were mailed to the respondents. The selection of respondents was done by stratified random sampling of the GPs in all 14 Malaysian states at both urban and rural levels. Out of a calculated number of 362 GPs targeted, 296 responses were received which represented a response rate of 81.7%. The respondents had a mean age of 50.7 years 165 (55.75%) were males and 131 (44.3%) were females. The rural respondents totalled 158 (53.4%) as compared to those from urban 138 (46.6%) areas. The outcomes observed were that GPs with PeKa B40 provider status, positive attitude towards health financing schemes, gatekeeper roles, and PeKa B40, were strongly associated with their acceptance and level of participation in the NHFS. The GPs possessed a positive attitude and were generally ready to participate in the NHFS, but the lower scores in knowledge levels would require definite education and training plans to further enhance their readiness. More incentives should be given to GPs to enrol as PeKa B40 providers. The results of this study should be strongly considered by the government in the efforts to engage the Malaysian private GPs in the forthcoming NHFS. Most importantly, the role of GPs as gatekeepers needed to be implemented, and the PeKa B40 scheme be greatly improved., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jamal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Antimicrobial resistance (AMR) is currently one of the global public health threats. Increased antibiotic consumption in humans, animals, and agriculture has contributed directly to the spread of AMR. Upper respiratory tract infections (URIs) are one of the most common conditions treated by antibiotics, even if unnecessary as in cases of viral infections and self-limited conditions which represent the most cases of URIs. Investigating physicians' knowledge, attitudes, and practice regarding antibiotic prescriptions in children with acute URIs may reflect the problem of antibiotic over prescription. This study aims to assess the problem in our community and provide information for further planning of appropriate interventions to optimize antibiotic prescriptions., Methods: This is a cross-sectional study for all non-specialized physicians dealing with acute upper respiratory tract infections (URIs) in pediatrics sittings in Assiut district, Egypt. We used a self-administered questionnaire to assess physicians' knowledge, attitudes, and practice. In addition, four clinical vignettes addressing different URI scenarios were included in the questionnaire to assess the patterns of antibiotic prescriptions in common cases., Results: Our study included 153 physicians whose mean age was 32.2 ± 8.7, most of whom were pediatric residents in different health institutes in Assiut district. They had good knowledge as out of the 17 knowledge questions,the mean number of correct answers was 12.4 ± 2.9. Regarding their attitudes, mean attitude scores for inappropriate antibiotic prescribing were low. However, of those scores, the responsibility of others had the highest score (3.8 ± 0.61). Prescribing practice in special conditions of URIs showed that 80% of participants prescribed antibiotics if fever continued for more than five days and 61.4% if the child had a yellowish or greenish nasal discharge. Among 612 clinical vignettes, 326 contained antibiotic prescriptions (53.3%), and appropriate antibiotic prescriptions represented only 8.3% overall., Conclusions: Physicians dealing with acute URIs in outpatients' clinics in the Assiut district have good knowledge about antibiotic use and resistance and demonstrate a good attitude toward appropriate antibiotic use. Although the percentage of inappropriate prescriptions in clinical vignettes in high, more research is required to investigate the factors of antibiotic inappropriate prescribing practice and non-adherence to guidelines. Also, it is essential to set up a national antibiotic stewardship program to improve antibiotic prescribing and contain antimicrobial resistance problems., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Even in a country with a tax-based healthcare financing system, health insurance can play an important role, especially in the management of chronic diseases with high disease and economic burden such as Type 2 Diabetes Mellitus (T2DM). The insurance coverage among T2DM patients in Malaysia is currently unclear. The aim of this study was to determine the insurance status of T2DM patients in public and private healthcare facilities in Malaysia, and the association between this status and patients' sociodemographic and economic factors., Methods: A cross-sectional study among T2DM patients seeking inpatient or outpatient treatment at a public tertiary hospital (Hospital Canselor Tuanku Muhriz) and a private tertiary hospital (Universiti Kebangsaan Malaysia Specialist Centre) in Kuala Lumpur between August 2019 and March 2020. Patients were identified via convenience sampling using a self-administered questionnaire. Data collection focused on identifying insurance status as the dependent factor while the independent factors were the patients' sociodemographic characteristics and economic factors., Results: Of 400 T2DM patients, 313 responded (response rate, 78.3%) and 76.0% were uninsured. About 69.6% of the respondents had low monthly incomes of

Background: Cyberbullying is a modern form of bullying that could be practiced electronically or on the internet. It is related to different mental health issues such as depression, which can affect both the cyberbully and the victim. Although a few studies have been conducted regarding the prevalence of cyberbullying and cyber-victimization among the younger generation in Qatar, no studies have been conducted among young adults despite studies showing that they are also prone to cyberbullying., Methods: This is a cross-sectional study to investigate the prevalence and the relationship between cyberbullying, cyber-victimization, and depression symptoms among Qatar University students. A self-administered close-ended electronic questionnaire was used to assess student's cyberbullying/cyber-victimization behaviors and depression symptoms. The Revised Cyberbullying Inventory scale (RCBI-II) and Patient Health questionnaire-9 (PHQ-9) were utilized to measure involvement in cyberbullying and depression symptoms, respectively. A total of 836 students participated in the study. Pearson Chi-Square test and binary logistic regression were conducted to analyze the data., Results: Results indicated the majority of students have been involved in cyberbullying as follows: 6.8% cyberbullies, 29.2% cybervictims, 35.8% cyberbully-victims, and 28.2% not involved in either. Approximately 50% of the students scored a ten or higher on the PHQ9 test indicating symptoms of depression. Moreover, significant associations were found between cyberbullying experiences and gender (p = 0.03), depression and gender (p = 0.046), and between cyberbullying experiences and depression (p<0.001)., Conclusion: Our findings indicate that among Qatar University students, cyberbullying and cyber-victimization are prevalent behaviors that could be associated with the high reported rates of depression symptoms., Competing Interests: The authors have declared that no competing interests exist.

Objectives: High-risk CXR features in COVID-19 are not clearly defined. We aimed to identify CXR features that correlate with severe COVID-19., Methods: All confirmed COVID-19 patients admitted within the study period were screened. Those with suboptimal baseline CXR were excluded. CXRs were reviewed by three independent radiologists and opacities recorded according to zones and laterality. The primary endpoint was defined as hypoxia requiring supplemental oxygen, and CXR features were assessed for association with this endpoint to identify high-risk features. These features were then used to define criteria for a high-risk CXR, and clinical features and outcomes of patients with and without baseline high-risk CXR were compared using logistic regression analysis., Results: 109 patients were included. In the initial analysis of 40 patients (36.7%) with abnormal baseline CXR, presence of bilateral opacities, multifocal opacities, or any upper or middle zone opacity were associated with supplemental oxygen requirement. Of the entire cohort, 29 patients (26.6%) had a baseline CXR with at least one of these features. Having a high-risk baseline CXR was significantly associated with requiring supplemental oxygen in univariate (odds ratio 14.0, 95% confidence interval 3.90-55.60) and multivariate (adjusted odds ratio 8.38, 95% CI 2.43-28.97, P = 0.001) analyses., Conclusion: We identified several high-risk CXR features that are significantly associated with severe illness. The association of upper or middle zone opacities with severe illness has not been previously emphasized. Recognition of these specific high-risk CXR features is important to prioritize limited healthcare resources for sicker patients., Competing Interests: The authors have declared that no competing interests exist.

This study mainly aims to identify the direct cost and economic burden of hypoglycemia for patients with type II diabetes mellitus in Malaysia. A cross-sectional study explored the cost incurred for hypoglycemia among patients admitted to University Kebangsaan Malaysia Medical Centre (UKMMC). The study covered patients aged 20-79 years hospitalized with a primary diagnosis of ICD-10 hypoglycemia and discharged between January 2010 and September 2015 according to the casemix database. A costing analysis was done through a step-down approach from the perspective of health providers. Cost data were collected for three levels of cost centers with the help of a hospital-costing template. The costing data from UKMMC were used to estimate the national burden of hypoglycemia among type II diabetics for the whole country. Of 244 diabetes patients admitted primarily for hypoglycemia to UKMMC, 52% were female and 88% were over 50 years old. The cost increased with severity. Managing a hypoglycemic case requires five days (median) of inpatient stay on average, with a range of 2-26 days, and costs RM 8,949 (USD 2,289). Of the total cost, 30% related to ward (final cost center), 16% to ICU, and 15% to pharmacy (secondary-level cost center) services. Considering that 3.2% of all admissions were hypoglycemia related, the total annual cost of hypoglycemia care for adult diabetics in Malaysia is estimated at RM 117.4 (USD 30.0) million, which translates to 0.5% of the Ministry of Health budget. Hypoglycemia imposes a substantial economic impact even without the direct and indirect cost incurred by patients and other cost of complications. Diabetic management needs to include proper diabetic care and health education to reduce episodes of hypoglycemia., Competing Interests: This research project is funded by Novo Nordisk Pharma (Malaysia) Sdn Bhd grant FF-2016-147 to SMA. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Human ether-à-go-go-related gene (Kv11.1, or hERG) is a potassium channel that conducts the delayed rectifier potassium current (IKr) during the repolarization phase of cardiac action potentials. hERG channels have a larger pore than other K+channels and can trap many unintended drugs, often resulting in acquired LQTS (aLQTS). R-roscovitine is a cyclin-dependent kinase (CDK) inhibitor that induces apoptosis in colorectal, breast, prostate, multiple myeloma, other cancer cell lines, and tumor xenografts, in micromolar concentrations. It is well tolerated in phase II clinical trials. R-roscovitine inhibits open hERG channels but does not become trapped in the pore. Two-electrode voltage clamp recordings from Xenopus oocytes expressing wild-type (WT) or hERG pore mutant channels (T623A, S624A, Y652A, F656A) demonstrated that compared to WT hERG, T623A, Y652A, and F656A inhibition by 200 μM R-roscovitine was ~ 48%, 29%, and 73% weaker, respectively. In contrast, S624A hERG was inhibited more potently than WT hERG, with a ~ 34% stronger inhibition. These findings were further supported by the IC50 values, which were increased for T623A, Y652A and F656A (by ~5.5, 2.75, and 42 fold respectively) and reduced 1.3 fold for the S624A mutant. Our data suggest that while T623, Y652, and F656 are critical for R-roscovitine-mediated inhibition, S624 may not be. Docking studies further support our findings. Thus, R-roscovitine's relatively unique features, coupled with its tolerance in clinical trials, could guide future drug screens., Competing Interests: The authors have declared that no competing interests exist.

Access to healthcare is essential in the pursuit of universal health coverage. Components of access are availability, accessibility (spatial and non-spatial), affordability and acceptability. Measuring spatial accessibility is common approach to evaluating access to health care. This study aimed to determine the availability and spatial accessibility of subsidised mammogram screening in Peninsular Malaysia. Availability was determined from the number and distribution of facilities. Spatial accessibility was determined using the travel impedance approach to represent the revealed access as opposed to potential access measured by other spatial measurement methods. The driving distance of return trips from the respondent's residence to the facilities was determined using a mapping application. The travel expenditure was estimated by multiplying the total travel distance by a standardised travel allowance rate, plus parking fees. Respondents in this study were 344 breast cancer patients who received treatment at 4 referral hospitals between 2015 and 2016. In terms of availability, there were at least 6 major entities which provided subsidised mammogram programs. Facilities with mammogram involved with these programs were located more densely in the central and west coast region of the Peninsula. The ratio of mammogram facility to the target population of women aged 40-74 years ranged between 1: 10,000 and 1:80,000. In terms of accessibility, of the 3.6% of the respondents had undergone mammogram screening, their mean travel distance was 53.4 km (SD = 34.5, range 8-112 km) and the mean travel expenditure was RM 38.97 (SD = 24.00, range RM7.60-78.40). Among those who did not go for mammogram screening, the estimated travel distance and expenditure had a skewed distribution with median travel distance of 22.0 km (IQR 12.0, 42.0, range 2.0-340.0) and the median travel cost of RM 17.40 (IQR 10.40, 30.00, range 3.40-240.00). Higher travel impedance was noted among those who lived in sub-urban and rural areas. In summary, availability of mammogram facilities was good in the central and west coast of the peninsula. The overall provider-to-population ratio was lower than recommended. Based on the travel impedance approach used, accessibility to subsidised mammogram screening among the respondents was good in urban areas but deprived in other areas. This study was a preliminary study with limitations. Nonetheless, the evidence suggests that actions have to be taken to improve the accessibility to opportunistic mammogram screening in Malaysia in pursuit of universal health coverage.

Background: Previous studies of compatibility of calcium chloride (CaCl2) and phosphates have not included particle counts in the range specified by the United States Pharmacopeia. Micro-flow imaging techniques have been shown to be comparable to light obscuration when determining particle count and size in pharmaceutical solutions., Objective: The purpose of this study was to do compatibility testing for parenteral nutrition (PN) solutions containing CaCl2 using dynamic light scattering and micro-flow imaging techniques., Methods: Solutions containing TrophAmine (Braun Medical Inc, Irvine, CA), CaCl2, and sodium phosphate (NaPhos) were compounded with and without cysteine. All solutions contained standard additives to neonatal PN solutions including dextrose, trace metals, and electrolytes. Control solutions contained no calcium or phosphate. Solutions were analyzed for particle size and particle count. Means of Z-average particle size and particle counts of controls were determined. Study solutions were compared to controls and United States Pharmacopeia (USP) Chapter 788 guidelines. The maximum amount of Phos that was compatible in solutions that contained at least 10 mmol/L of Ca in 2.5% amino acids (AA) was determined. Compatibility of these solutions was verified by performing analyses of 5 repeats of these solutions. Microscopic analyses of the repeats were also performed., Results: Amounts of CaCl2 and NaPhos that were compatible in solutions containing 1.5%, 2%, 2.5%, and 3% AA were determined. The maximum amount of NaPhos that could be added to TrophAmine solutions of > = 2.5% AA containing at least 10 mmol/L of CaCl2 was 7.5 mmol/L. Adding 50 mg/dL of cysteine increased the amount of NaPhos that could be added to solutions containing 10 mmol/L of CaCl2 to 10 mmol/L., Conclusion: Calcium chloride can be added to neonatal PN solutions containing NaPhos in concentrations that can potentially provide an intravenous intake of adequate amounts of calcium and phosphorus.

The ability of the antineoplastic agent epirubicin to induce aneuploidy and meiotic delay in the somatic and germinal cells of male mice was investigated by fluorescence in situ hybridization assay using labeled DNA probes and BrdU-incorporation assay. Mitomycin C and colchicine were used as positive controls for clastogen and aneugen, respectively, and these compounds produced the expected responses. The fluorescence in situ hybridization assay with a centromeric DNA probe for erythrocyte micronuclei showed that epirubicin is not only clastogenic but also aneugenic in somatic cells in vivo. By using the BrdU-incorporation assay, it could be shown that the meiotic delay caused by epirubicin in germ cells was approximately 48 h. Disomic and diploid sperm were shown in epididymal sperm hybridized with DNA probes specific for chromosomes 8, X and Y after epirubicin treatment. The observation that XX- and YY-sperm significantly prevailed over XY-sperm indicates missegregation during the second meiotic division. The results also suggest that earlier prophase stages contribute less to epirubicin-induced aneuploidy. Both the clastogenic and aneugenic potential of epirubicin can give rise to the development of secondary tumors and abnormal reproductive outcomes in cured cancer patients and medical personnel exposed to epirubicin.

The Zonula Occludens proteins ZO-1 and ZO-2 are cell-cell junction-associated adaptor proteins that are essential for the structural and regulatory functions of tight junctions in epithelial cells and their absence leads to early embryonic lethality in mouse models. Here, we use the embryoid body, an in vitro peri-implantation mouse embryogenesis model, to elucidate and dissect the roles ZO-1 and ZO-2 play in epithelial morphogenesis and de novo tight junction assembly. Through the generation of individual or combined ZO-1 and ZO-2 null embryoid bodies, we show that their dual deletion prevents tight junction formation, resulting in the disorganization and compromised barrier function of embryoid body epithelial layers. The disorganization is associated with poor microvilli development, fragmented basement membrane deposition and impaired cavity formation, all of which are key epithelial tissue morphogenetic processes. Expression of Podocalyxin, which positively regulates the formation of microvilli and the apical membrane, is repressed in embryoid bodies lacking both ZO-1 and ZO-2 and this correlates with an aberrant submembranous localization of Ezrin. The null embryoid bodies thus give an insight into how the two ZO proteins influence early mouse embryogenesis and possible mechanisms underlying the embryonic lethal phenotype.

Aims: Development of metabolic syndrome is associated with impaired cardiac performance, mitochondrial dysfunction and pro-inflammatory cytokine increase, such as the macrophage migration inhibitory factor MIF. Depending on conditions, MIF may exert both beneficial and deleterious effects on the myocardium. Therefore, we tested whether pharmacological inhibition of MIF prevented or worsened metabolic syndrome-induced myocardial dysfunction., Methods and Results: C57BL/6J mice were fed for ten weeks with 60% fat-enriched diet (HFD) or normal diet (ND). MIF inhibition was obtained by injecting mice twice a week with ISO-1, for three consecutive weeks. Then, triglycerides, cholesterol, fat mass, glucose intolerance, insulin resistance, ex vivo cardiac contractility, animal energetic substrate utilization assessed by indirect calorimetry and mitochondrial respiration and biogenesis were evaluated. HFD led to fat mass increase, dyslipidemia, glucose intolerance and insulin resistance. ISO-1 did not alter these parameters. However, MIF inhibition was responsible for HFD-induced cardiac dysfunction worsening. Mouse capacity to increase oxygen consumption in response to exercise was reduced in HFD compared to ND, and further diminished in ISO-1-treated HFD group. Mitochondrial respiration was reduced in HFD mice, treated or not with ISO-1. Compared to ND, mitochondrial biogenesis signaling was upregulated in the HFD as demonstrated by mitochondrial DNA amount and PGC-1α expression. However, this increase in biogenesis was blocked by ISO-1 treatment., Conclusion: MIF inhibition achieved by ISO-1 was responsible for a reduction in HFD-induced mitochondrial biogenesis signaling that could explain majored cardiac dysfunction observed in HFD mice treated with MIF inhibitor.

Aims: Metabolic syndrome induces cardiac dysfunction associated with mitochondria abnormalities. As low levels of carbon monoxide (CO) may improve myocardial and mitochondrial activities, we tested whether a CO-releasing molecule (CORM-3) reverses metabolic syndrome-induced cardiac alteration through changes in mitochondrial biogenesis, dynamics and autophagy., Methods and Results: Mice were fed with normal diet (ND) or high-fat diet (HFD) for twelve weeks. Then, mice received two intraperitoneal injections of CORM-3 (10 mg x kg(-1)), with the second one given 16 hours after the first. Contractile function in isolated hearts and mitochondrial parameters were evaluated 24 hours after the last injection. Mitochondrial population was explored by electron microscopy. Changes in mitochondrial dynamics, biogenesis and autophagy were assessed by western-blot and RT-qPCR. Left ventricular developed pressure was reduced in HFD hearts. Mitochondria from HFD hearts presented reduced membrane potential and diminished ADP-coupled respiration. CORM-3 restored both cardiac and mitochondrial functions. Size and number of mitochondria increased in the HFD hearts but not in the CORM-3-treated HFD group. CORM-3 modulated HFD-activated mitochondrial fusion and biogenesis signalling. While autophagy was not activated in the HFD group, CORM-3 increased the autophagy marker LC3-II. Finally, ex vivo experiments demonstrated that autophagy inhibition by 3-methyladenine abolished the cardioprotective effects of CORM-3., Conclusion: CORM-3 may modulate pathways controlling mitochondrial quality, thus leading to improvements of mitochondrial efficiency and HFD-induced cardiac dysfunction.

Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC) transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA) suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2), KG-1 (ABCB1) and HepG2 cells (ABCB1 and ABCG2). Interestingly, although side population (SP) cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG-1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells.