Association between Fluoride Exposure and Blood pressure

Objectives: This study investigated whether fluoride was associated with an increased prevalence of high blood pressure (BP) among adolescents in the United States. Methods: The study sample consisted of 2015–2016 National Health and Nutrition Examination Survey participants aged 13–17 years. Independent-samples t-tests, Chi-square tests, and regression models were used to analyze the data. Results: A total of 814 participants met the study criteria. The findings showed that the proportion of patients with high levels of water or plasma fluoride in the high BP group was higher than that in the normal BP group. However, after adjusting for sociodemographic covariates, neither water nor plasma fluoride levels were significantly associated with a high BP. Conclusions: This study did not find an association between either water or plasma fluoride levels and high BP. Further study is needed to exclude a dose dependent effect at higher levels of fluoride

Potent efficacy of metronomic topotecan and pazopanib combination therapy in preclinical models of primary or late stage metastatic triple-negative breast cancer

Metronomic chemotherapy has shown promising activity in numerous preclinical studies and also some phase II clinical studies involving various tumor types, and is currently undergoing phase III trial evaluation. Triple-negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and very poor prognosis following progression after standard chemotherapeutic regimens. Herein, we evaluated the potential therapeutic impact and molecular mechanisms of topotecan administered in a continuous low-dose metronomic (LDM) manner, alone or in concurrent combination with pazopanib, an antiangiogenic tyrosine kinase inhibitor (TKI), in a triple-negative, primary and metastatic breast cancer orthotopic model; potential molecular mechanisms of efficacy were also studied, especially the impact of hypoxic conditions. The combination of metronomic topotecan and pazopanib significantly enhanced antitumor activity compared to monotherapy with either drug and prolonged survival, even in the advanced metastatic survival setting, with a marked decrease in tumor vascularity, proliferative index, and the induction of apoptosis. Significant changes in tumor angiogenesis, cancer cell proliferation, apoptosis, HIF1α levels, HIF-1 target genes and ABCG2 were found both in vitro and in tumor tissue. Notably, the pazopanib and metronomic topotecan combination treatment inhibited expression of HIF1α and ABCG2 genes in cells grown under hypoxic conditions, and this was associated with an increased intracellular concentration of the active form of topotecan. Our results suggest a potential novel therapeutic option for the treatment of metastatic triple-negative breast cancer patients

Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones stood out for their ability to fully rescue SH-SY5Y human neuroblastoma cells against both H2O2- and Aβ1-42-induced cell death. Cholinesterase inhibition was also evaluated, and modest inhibitory activities were found. This work highlights the potential of C-glucosylflavones as neuroprotective agents, and presents the p-morpholinyl C-glucosylflavone 37, which did not show any cytotoxicity towards HepG2 and Caco-2 cells at 100 μM, as a new lead structure for further development against AD.Fundação para a Ciência e a Tecnologia-UID/Multi/0612/2019Unión Europea-D3i4AD), FP7-PEOPLE-2013-IAPP, GA 61234

University Students’ Communication and Employability Skills: Mismatch Perspectives of Students, Lecturers, and Employers in Sarawak, Malaysia

In Malaysia, graduate unemployability is a problem that is often highlighted. Studies have shown that graduates lack soft skills, such as problem solving, English language proficiency, and communication skills, which contribute to the issue of unemployability. However, these studies have not investigated employability skills from all three perspectives of students, lecturers, and employers to understand whether students are developing the necessary skills to be more employable, and whether lecturers are getting it right when preparing their students for the job market. Therefore, this study fills in the gap by comparing university students’ communication and employability skills from the perspectives of students, lecturers, and employers. The study aimed to determine students’ ratings of communicative ability and employability skills, and how these ratings match those of the lecturers and employers, and to compare the ranking of the importance of these skills by lecturers and employers. The questionnaire data were collected from 123 students, 26 lectures, and 26 employers in Sarawak, Malaysia. The findings showed that the students rated themselves more highly on reading and writing, and employability skills than on listening and speaking skills. The lecturers and employers ranked employability skills as more important than communication skills. They were consistent in the ranking of interpersonal skills and presentation skills as the top communication skills. The top employability skills were time management skills, leadership qualities, managing personnel, managing resources, teamwork spirit, planning, organising, controlling and evaluation skills, and problem-solving aptitude. However, lecturers prioritised teamwork spirit while employers prioritised problem-solving aptitude. However, none of the reading and writing skills were among the top 10 skills expected of graduates entering the workplace. In concluding the study, the overall findings indicated that the students and lecturers overrated the students’ readiness for the workplace

A National Study Exploring the Association Between Fluoride Levels and Dental Fluorosis

Importance: While the effects of fluoride on health have been widely researched, fewer high-quality studies examine the association of fluoride levels in water and dental fluorosis. Objective: To investigate the association between fluoride exposure from drinking water and dental fluorosis. Design, setting, and participants: This cross-sectional study used the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES) data (January 1, 2013, through December 31, 2016). NHANES uses a complex sampling technique to develop nationally representative sample estimates of the US population that consists of interviews and physical assessments. Children and adolescents aged 6 to 15 years were included because NHANES contains their data for all 3 forms of fluoride measures: plasma fluoride levels, water levels of fluoride, and dietary fluoride supplementation. Data were analyzed from January 1 to April 30, 2023. Exposures: Water and plasma fluoride levels were measured by laboratory personnel. Dietary fluoride supplement data were self-reported. Main outcomes and measures: The Dean's Fluorosis Index was used to evaluate fluorosis status for each tooth. The dental fluorosis severity value was based on the second most affected tooth. Independent variables included plasma and water fluoride concentrations and dietary fluoride supplementation. An independent samples t test was used to compare fluoride exposures between groups, and Pearson correlation assessed the association between plasma and water fluoride levels. To assess whether fluoride exposures were associated with dental fluorosis, logistic regression analyses were conducted. Results: There were 1543 participants in the 2013-2014 NHANES cycle (weighted proportion male, 51.9%; mean [SD] age, 11.0 [2.7] years) and 1452 in the 2015-2016 cycle (weighted proportion male, 52.6%; mean [SD] age, 11.1 [2.8] years). A weighted 87.3% exhibited some degree of fluorosis in the 2013-2014 cycle and 68.2% in the 2015-2016 cycle. Higher fluoride levels in water and plasma were significantly associated with higher odds of dental fluorosis (adjusted odds ratios, 2.378 [95% CI, 2.372-2.383] in the 2013-2014 cycle and 1.568 [95% CI, 1.564-1.571] in the 2015-2016 cycle). Conclusions and relevance: The findings of this cross-sectional study suggest that exposure to higher concentrations of fluoride in water and having higher plasma levels of fluoride were associated with a greater risk of dental fluorosis. Further research can help policy makers develop policies that balance substantial caries prevention with the risk of dental fluorosis.</p

MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6–p47phox–oxidative stress pathway in neutrophils

Objectives Chronic-plus-binge ethanol feeding activates neutrophils and exacerbates liver injury in mice. This study investigates how recent excessive drinking affects peripheral neutrophils and liver injury in alcoholics, and how miR-223, one of the most abundant microRNAs (miRNAs) in neutrophils, modulates neutrophil function and liver injury in ethanol-fed mice. Designs Three hundred alcoholics with (n=140) or without (n=160) recent excessive drinking and 45 healthy controls were enrolled. Mice were fed an ethanol diet for 10 days followed by a single binge of ethanol. Results Compared with healthy controls or alcoholics without recent drinking, alcoholics with recent excessive drinking had higher levels of circulating neutrophils, which correlated with serum levels of alanine transaminase (ALT) and aspartate transaminase (AST). miRNA array analysis revealed that alcoholics had elevated serum miR-223 levels compared with healthy controls. In chronic-plus-binge ethanol feeding mouse model, the levels of miR-223 were increased in both serum and neutrophils. Genetic deletion of the miR-223 gene exacerbated ethanol-induced hepatic injury, neutrophil infiltration, reactive oxygen species (ROS) and upregulated hepatic expression of interleukin (IL)-6 and phagocytic oxidase (phox) p47phox. Mechanistic studies revealed that miR-223 directly inhibited IL-6 expression and subsequently inhibited p47phox expression in neutrophils. Deletion of the p47phox gene ameliorated ethanol-induced liver injury and ROS production by neutrophils. Finally, miR-223 expression was downregulated, while IL-6 and p47phox expression were upregulated in peripheral blood neutrophils from alcoholics compared with healthy controls. Conclusions miR-223 is an important regulator to block neutrophil infiltration in alcoholic liver disease and could be a novel therapeutic target for the treatment of this malady

University Students’ Communication and Employability Skills: Mismatch Perspectives of Students, Lecturers, and Employers in Sarawak, Malaysia

In Malaysia, graduate unemployability is a problem that is often highlighted. Studies have shown that graduates lack soft skills, such as problem solving, English language proficiency, and communication skills, which contribute to the issue of unemployability. However, these studies have not investigated employability skills from all three perspectives of students, lecturers, and employers to understand whether students are developing the necessary skills to be more employable, and whether lecturers are getting it right when preparing their students for the job market. Therefore, this study fills in the gap by comparing university students’ communication and employability skills from the perspectives of students, lecturers, and employers. The study aimed to determine students’ ratings of communicative ability and employability skills, and how these ratings match those of the lecturers and employers, and to compare the ranking of the importance of these skills by lecturers and employers. The questionnaire data were collected from 123 students, 26 lectures, and 26 employers in Sarawak, Malaysia. The findings showed that the students rated themselves more highly on reading and writing, and employability skills than on listening and speaking skills. The lecturers and employers ranked employability skills as more important than communication skills. They were consistent in the ranking of interpersonal skills and presentation skills as the top communication skills. The top employability skills were time management skills, leadership qualities, managing personnel, managing resources, teamwork spirit, planning, organising, controlling and evaluation skills, and problem-solving aptitude. However, lecturers prioritised teamwork spirit while employers prioritised problem-solving aptitude. However, none of the reading and writing skills were among the top 10 skills expected of graduates entering the workplace. In concluding the study, the overall findings indicated that the students and lecturers overrated the students’ readiness for the workplace

Employability and Communication Skills : Triangulating Views of Employers, Lecturers and Undergraduates

Employability skills are known as soft skills and transferrable skills. Employability refers to skills, understandings, and personal attributes that increase graduates’ chances of employment and success in their chosen occupations (Yorke, 2004). Some of the skills listed under employability skills are resourcefulness, adaptability, and flexibility which are not only needed for adapting to work situations (Curtis & McKenzie, 2002). In a VUCA (volatility, uncertainty, complexity, and ambiguity) environment, there is a limit to what universities can equip graduates with, and they need to be able to continue learning to adjust to new situations and demands. According to the Secretary’s Commission on Achieving Necessary Skills (SCANS) in the USA (1992), employability skills can be divided into four clusters of basic skills, thinking skills, personal qualities, and workplace competence. These skills would give them an edge during interviews and increase their chances of getting employed. Malaysia has been experiencing graduate unemployability. Approximately 60% of graduates remain unemployed for minimum of a year after graduation (“Graduate Employability”, 2020). There are many factors that contribute to graduate unemployability such as lack of experience, language proficiency, communication skills, problem-solving skills, and critical thinking skills (Hanapi & Nordin, 2014; Lim et al., 2016; Nooriah & Zakiah, 2017; Ooi & Ting, 2017). Employers often specify good communication skills and interpersonal skills as top requirements in job advertisements (Bakar et al., 2007; Ooi & Ting, 2017). However, graduates lack problem solving skills, communication skills (Hanapi & Nordin, 2014) and technical knowledge (Lim et al., 2016). In a knowledge-based economy, employees need to be independent and self-motivated (Menand, 2014) to acquire the necessary knowledge, information and high skill levels to cope with the fast pace of technological change. There is currently scarcity of findings on whether universities and students are preparing themselves appropriately to meet the expectations of employers. The study investigated importance of employability and communication skills based on the views of employers, lecturers and students. The research questions were: (1) how good are university students in their employability and communication skills? and (2) do employers and lecturers agree on the most important skills an effective employee should have? The descriptive study involved the use of a questionnaire on employability skills and language skills (listening and speaking, reading and writing). The items were formulated using a five-point rating scale of (1) not at all, (2) to some extent, (3) just enough, (4) to a reasonable extent, and (5) to a great extent. In addition, the questionnaire required lecturers and employers to select the top 10 skills out of the 25 skills listed. The data were collected from 123 students, 26 lecturers from a public university, and 26 employers in Sarawak, East Malaysia. The students were mostly female (74.80% female, 25.20% male) and had weak to moderate language proficiency, measured using the Malaysian University English Test (MUET). There were slightly more males among lecturers (12 female, 14 male) and employers (11 female, 15 male). The average years of work experience for lecturers was 8.7 (range: 1-25) and for employers, the average was 5.6 (range: 1-15). For the analysis, means and frequencies were calculated for comparison of the three perspectives on the importance of communication and employability skills. The results showed that there was a difference among employers, lecturers, and students in their ratings of how good university students are in their employability and communication skills. The students overrated themselves in all three set of skills. Based on the mean scores, the students rated themselves as having a moderate level of employability (M=3.74), reading and writing skills (M=3.75), and listening and speaking skills (M=3.61). The lecturers rated the university students as having a moderate level of skills as well, but the mean scores were slightly lower than the students’ (employability, M= 3.54; reading and writing skills, M=3.49; listening and speaking skills, M=3.29). To the employers, only the fresh graduates’ listening and speaking skills were moderate but on the weak side (M=3.15). The employers found the fresh graduates’ reading and writing skills (M=2.97) and listening and speaking skills (M=2.92) to be slightly weak. Interestingly, the students and lecturers rated the graduates’ employability skills to be moderate but the employers considered them to be weak. Another contrast was the students’ listening and speaking skills, which the students and lecturers considered to be the lowest level, compared to employability and reading and writing skills. However, the employers considered the fresh graduates’ listening and speaking skills to be better than the other two skills. This comparison shows that there is a mismatch in the ratings of university students’ employability and communication skills given by employers, lecturers, and students. The employers’ expectation was higher than the lecturers’. In other words, most employers expect students to be ready to handle the demands of the workforce upon graduation but sadly, most graduates fell short of their expectations. The employers may feel that they have to spoon feed the graduates on various matters upon graduation and they prefer employees who have a strong set of communication and employability skills. Next, the results on the ranking of the important skills an effective employee should have also showed a mismatch in the perspectives of employers and lecturers. To the employers, the top two skills were time management and problem-solving aptitude, both of which were employability skills. To the lecturers, the top two skills were leadership qualities and teamwork spirit, which were also employability skills. The employers prioritised skills for efficient handling of work situations to meet deadlines but the lecturers focussed on skills for the completion of group work. The mismatch shows that lecturers and universities may have overlooked the need to train students to be versatile to solve problems and complete projects on time. Indeed, students often submit work late and are not independent enough to resolve questions concerning their projects on their own, and constantly have to consult lecturers. To increase graduate employability, universities need to collaborate strategically with the industry to resolve the mismatch of expectations, as other Malaysian studies have also found a mismatch (Nadarajah, 2021; Nesaratnam et al., 2020). However, because of the fast-changing work environment, students need to develop lifelong learning skills so that they can develop their expertise, knowledge base, and a lifelong learning mindset to stay relevant. References Bakar, A. R., Mohamed, S., & Hanafi, I. (2007). Employability skills: Malaysian employers perspectives. The International Journal of Interdisciplinary Social Sciences, 2(1), 263-274. Curtis, D. D., & McKenzie, P. (2002). Employability skills for Australian industry: Literature review and framework development. http://www.voced.edu.au/content/ngv33428 Graduate employability: A priority of the Education Ministry. (2020, February 18). News Straits Times. https://www.nst.com.my/news/nation/2020/02/566731/graduate-employability-priority-education-ministry Hanapi, Z., & Nordin, M. S. (2014). Unemployment among Malaysia graduates: Graduates’ attributes, lecturers’ competency and quality of education. Procedia - Social and Behavioral Sciences, 112, 1056-1063. https://doi.org/10.1016/j.sbspro.2014.01.1269 Lim, Y. M, Teck, H. L., Ching, S. Y., & Chui, C. L. (2016). Employability skills, personal qualities, and early employment problems of entry-level auditors: Perspectives from employers, lecturers, auditors, and students. Journal of Education for Business, 91(4), 185-192. https://doi.org/10.1080/08832323.2016.1153998 Menand, H. (2014). Critical instruction, student achievement, and nurturing of global citizens: Global and comparative education in context. In S. A. Lawrence (Ed.), Critical practice in P-12 education (pp. 1-23). Hershey: Information Science Reference. Nadarajah, J. (2021). Measuring the gap in employability skills among Malaysian graduates. International Journal of Modern Trends in Social Sciences, 4(15), 81-87. https://doi.org/10.35631/IJMTSS.415007 Nesaratnam, S., Salleh, W. H. W., Foo, Y. V., Hisham, W. M. W. S. W. (2020). Enhancing English proficiency and communication skills among Malaysian graduates through training and coaching. International Journal of Learning and Development, 10(4), 1-12. https://doi.org/10.5296/ijld.v10i4.17875 Nooriah, Y., & Zakiah, J. (2017). Development of graduates employability: The role of university and challenges. Jurnal Personalia Pelajar, 20, 15-32. Ooi, K. B., & Ting, S. H. (2015). Employers’ emphasis on technical skills and soft skills in job advertisements. The English Teacher, 44(1), 1-12. Secretary’s Commission on Achieving Necessary Skills (SCANS) (1992). Learning a living: a blueprint for high performance. A SCANS report for America 2000. Washington: U.S. Department of Labour. Yorke, M. (2004). Employability in higher education: what it is – what it is not. York: The Higher Education Academy/ESECT