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Introduction: The incidence of angiotensin-converting enzyme inhibitors (ACEi)-induced cough has been reported between 5% and 30% but is unknown in Malaysia. This study aimed to determine the incidence of ACEi-induced cough and its associated factors in a public primary care clinic in Malaysia. Methods: A retrospective review of electronic medical records of patients who were initiated ACEi between January 1, 2015, and December 31, 2015, and reviewed until July 31, 2016. A total of 1,091 patients were newly prescribed ACEi, and 394 patients were eligible for this study. We excluded patients who defaulted follow-ups with no further clinic visits before July 31, 2016, were transferred to the clinic without the recorded date of ACEi initiation, were transferred to other clinics during the study period, were followed up at other clinics and attended the study clinic for a short period, or were given only a stat dose of ACEi. Results: Among the 394 patients initiated on ACEi, 225 (57.1%) were male, 369 (93.7%) were Malay, 376 (95.4%) had hypertension, and 192 (48.7%) had diabetes. The incidence of ACEi-induced cough was 24.1%, and 42 (10.7%) patients developed cough on the day of therapy initiation. There was no association between age, gender, ethnicity, type of ACEi, and cough. Conclusion: Approximately one quarter of patients developed cough after ACEi initiation, and approximately half of them developed cough within 1 week of ACEi initiation. Doctors should consider early follow-up for patients initiated on ACEi therapy to ensure adherence, quality of life, and minimise unnecessary treatment.

Abstract Background Zoonoses among household pets are recognized as disease and infections transmitted between animals and humans. World Health Organization‐estimated zoonotic diseases have contributed about one billion cases of illness and millions of mortalities every year. Despite the emerging and re‐emerging zoonotic disease, most pet owners are unaware of the risks posed by their pets. As there are a lack of studies assessing infections at home, this study aimed to develop and validate a cognitive, affective and behaviour questionnaire (CAB‐ZDQ) to assess household pets’ zoonotic diseases. Methods This paper covers detailed explanation on the various developmental and validation process stages of the CAB zoonotic disease questionnaire development. The development phase comprised thorough literature search, focus group discussion, expert panel assessment and review. The validation process included pre‐test and pilot testing, data analysis of results, analysis of internal consistency and the development of the final version of the questionnaire. Participants selected represented main ethnicities, gender, levels of education and population type (urban/rural) in the Klang Valley area. Results The items in the questionnaire has undergone various changes in structurally and linguistically. The final refined CAB questionnaire consists of 14 items cognitive (no items removed at pilot phase), nine items affective (one item removed at pilot phase) and five items behaviour (no items removed from pre‐test phase), respectively. Reliability analysis revealed Cronbach's alpha values were 0.700 (cognitive) and 0.606 (affective) which indicated good internal consistency after item reduction. Conclusions The developed questionnaire has proved its feasibility in assessing the Malaysian general population cognitive, affective and behavior regarding the household pets’ zoonotic diseases.

Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate citrullinated proteins. Apart from carrying out citrullination in the periodontium, the bacterium is found capable of citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. Studies have suggested that both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, atherosclerosis, and Alzheimer’s disease. Thus, inhibition of these virulence factors not only can mitigate periodontitis, but also can provide new therapeutic solutions for systematic diseases involving bacterial citrullination. Herein, we described both these proteins in terms of their unique structural conformations and biological relevance to different human diseases. Moreover, investigations of inhibitory actions on the enzymes are also enumerated. New approaches for identifying inhibitors for peptidyl arginine deiminase through drug repurposing and virtual screening are also discussed.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by decreased synaptic transmission and cerebral atrophy with appearance of amyloid plaques and neurofibrillary tangles. Cognitive, functional, and behavioral alterations are commonly associated with the disease. Different pathophysiological pathways of AD have been proposed, some of which interact and influence one another. Current treatment for AD mainly involves the use of therapeutic agents to alleviate the symptoms in AD patients. The conventional single-target treatment approaches do not often cause the desired effect in the disease due to its multifactorial origin. Thus, multi-target strategies have since been undertaken, which aim to simultaneously target multiple targets involved in the development of AD. In this review, we provide an overview of the pathogenesis of AD and the current drug therapies for the disease. Additionally, rationales of the multi-target approaches and examples of multi-target drugs with pharmacological actions against AD are also discussed.

Although e-Portfolio is acknowledged as one of the powerful pedagogical practices that enhance learning in higher education (HE), not much is known about the types of social media (SM) utilized as e-Portfolios and the benefits for students. This literature analysis, using directed content analysis, aims to explore the above vacuum. The research questions in this study are: (1) In what ways do the SM as e-Portfolios benefit students in HE?, (2) To what extent are the benefits of SM as e-Portfolios comparable to those of conventional e-Portfolios? ,and (3) What are the drawbacks that practitioners and researchers need to be concerned with? Findings indicate that blogs are the most popular SM used as e-Portfolios to support learning, followed by social networking sites and collaborative projects. The study yields 13 advantages and 12 drawbacks when SM is manipulated as e-Portfolios. These findings conclude that the use of SM as e-Portfolios has a great potential in supporting students' learning and development by providing an environment for them to learn meaningfully from their experiences and engage in critical reflections and dialogues that allow them to gain new knowledge and valuable insights and thus, improve their skills. A pedagogical framework for the planning and implementation of SM as e-Portfolios is suggested based on the findings and aims of the papers that were reviewed.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM).

Human A3 adenosine receptor hA3AR has been implicated in gastrointestinal cancer, where its cellular expression has been found increased, thus suggesting its potential as a molecular target for novel anticancer compounds. Observation made in our previous work indicated the importance of the carbonyl group of amide in the indolylpyrimidylpiperazine (IPP) for its human A2A adenosine receptor (hA2AAR) subtype binding selectivity over the other AR subtypes. Taking this observation into account, we structurally modified an indolylpyrimidylpiperazine (IPP) scaffold, 1 (a non-selective adenosine receptors’ ligand) into a modified IPP (mIPP) scaffold by switching the position of the carbonyl group, resulting in the formation of both ketone and tertiary amine groups in the new scaffold. Results showed that such modification diminished the A2A activity and instead conferred hA3AR agonistic activity. Among the new mIPP derivatives (3−6), compound 4 showed potential as a hA3AR partial agonist, with an Emax of 30% and EC50 of 2.89 ± 0.55 μM. In the cytotoxicity assays, compound 4 also exhibited higher cytotoxicity against both colorectal and liver cancer cells as compared to normal cells. Overall, this new series of compounds provide a promising starting point for further development of potent and selective hA3AR partial agonists for the treatment of gastrointestinal cancers.

In this paper a correction factor for Jennrich’s statistic is introduced in order to be able not only to test the stability of correlation structure, but also to identify the time windows where the instability occurs. If Jennrich’s statistic is only to test the stability of correlation structure along predetermined non-overlapping time windows, the corrected statistic provides us with the history of correlation structure dynamics from time window to time window. A graphical representation will be provided to visualize that history. This information is necessary to make further analysis about, for example, the change of topological properties of minimal spanning tree. An example using NYSE data will illustrate its advantages.

Although e-Portfolio is acknowledged as one of the powerful pedagogical practices that enhance learning in higher education (HE), not much is known about the types of social media (SM) utilized as e-Portfolios and the benefits for students. This literature analysis, using directed content analysis, aims to explore the above vacuum. The research questions in this study are: (1) In what ways do the SM as e-Portfolios benefit students in HE? (2) To what extent are the benefits of SM as e-Portfolios comparable to those of conventional e-Portfolios? and (3) What are the drawbacks that practitioners and researchers need to be concerned with? Findings indicate that blogs are the most popular SM used as e-Portfolios to support learning, followed by social networking sites and collaborative projects. The study yields 13 advantages and 12 drawbacks when SM is manipulated as e-Portfolios. These findings conclude that the use of SM as e-Portfolios has a great potential in supporting students' learning and development by providing an environment for them to learn meaningfully from their experiences and engage in critical reflections and dialogues that allow them to gain new knowledge and valuable insights and thus, improve their skills. A pedagogical framework for the planning and implementation of SM as e-Portfolios is suggested based on the findings and aims of the papers that were reviewed. [ABSTRACT FROM AUTHOR]