Development of microwave system for extraction of essential oils from Mesua ferrea L. leaves and Jasminum samhac flowers

A microwave extraction system (MES) was developed for the extraction of essential oils from Mesua ferrea L. leaves and Jasminum sambac flowers. The performance of MES was compared with the conventional extraction method (CEM) for dry distillation (DD), wet distillation (WD), hydro distillation (HD) and steam distillation (SD) in terms of rapidity, quality and quantity of yield and its efficiency. Mesua ferrea L. extracted by HD contributed 0.035% of yield, WD 0.029%, DD 0.024% and SD 0.013%. For Jasminum sambac, DD contributed 0.10%, WD 0.06% while SD and HD both contributed 0.02%, respectively. Although more compounds were detected in CEM extract, substantial higher amounts of odoriferous compounds were present in MES extract. The project has successfully proved that MES is more efficient than CEM in terms of rapidity, quality and quantity of yield

Cellular Delivery and Biological Activity of Antisense Oligonucleotides Conjugated to a Targeted Protein Carrier

Targeted delivery can potentially improve the pharmacological effects of antisense and siRNA oligonucleotides. Here we describe a novel bioconjugation approach to the delivery of splice-shifting antisense oligonucleotides (SSOs). The SSOs are linked to albumin via reversible S-S bonds. The albumin is also conjugated with polyethylene glycol (PEG) chains that terminate in an RGD ligand that selectively binds the αvβ3 integrin. As a test system we utilized human melanoma cells that express the αvβ3 integrin and that also contain a luciferase reporter gene that can be induced by delivery of SSOs to the cell nucleus. The RGD-PEG-SSO-albumin conjugates were endocytosed by the cells in an RGD-dependent manner; using confocal fluorescence microscopy evidence was obtained that the SSOs accumulate in the nucleus. The conjugates were able to robustly induce luciferase expression at concentrations in the 25−200nM range. At these levels little short-term or long-term toxicity was observed. Thus the RGD-PEG-Albumin conjugates may provide an effective tool for targeted delivery of oligonucleotides to certain cells and tissues

Total replacement of fish meal by enriched-fatty acid Hermetia illucens meal did not substantially affect growth parameters or innate immune status and improved whole body biochemical quality of Nile tilapia juveniles

The study was designed to evaluate the effects of total remplacement of fish meal (FM) and fish oil (FO) by vegetable oil and black soldier fly (BSF) larval meal enriched with fatty acids (FAs) in Nile tilapia juveniles. Fish were fed a FMFO control diet compared to a non-FA-enriched BSF diet (BSF/T0) and diets enriched in linolenic acid-ALA (BSF/T1) or in eicosapentanoic acid-EPA (BSF/T2). After 59 days, the BSF diets did not affect growth except for a decrease by the BSF/T1 diet. However, protein utilization and digestibility were reduced by all the BSF diets. FA-enriched diets did not improve the digestive enzyme activities or immune parameters, while lysozyme and ACH50 values were increased by the BSF/T0 diet. Levels of polyunsaturated FAs in the whole body of fish fed ALA or EPA-enriched BSF diets were comparable to those of FMFO controls. The results demonstrate that BSF meal can totally replace FM without substantially effect on growth or innate immune status. The decrease in fish carcass FA quality induced by the BSF meal can be prevented by a well defined protocol for PUFA enrichment. Nonetheless, investigation of the long-term effects of the BSF meal use during the ongrowing phase is still needed

5A's and 3A's Adolescent Smoking Interventions as Nicotine Dependence Endgame Initiatives in Sarawak, Malaysia

Anti-smoking initiatives in Malaysia have the potential to reduce adolescent smoking, but their effectiveness and the need for research support remain important considerations. This study aimed to examine the efficacy of two smoking cessation interventions, the 5A's and 3A's, in reducing smoking among male adolescents in Samarahan, Sarawak. From September 2020 to June 2021, twelve communities were randomly assigned to the 5A's, 3A's, or control groups. A total of 519 participants aged 13-17 years provided data on demographics, smoking habits, nicotine dependency, motivation, carbon monoxide levels, and monthly cigarette consumption. The interventions' effectiveness was evaluated at 1, 3, 6 and 9 months. Analysis of covariance revealed no significant main effects of time or group on nicotine dependence, although age had a significant effect. Post hoc analyses showed significant group differences at multiple time points. For motivation, there was a significant main effect of time, with Group 5A consistently demonstrating higher means. Significant group differences were observed at specific time points. Analysis of carbon monoxide levels indicated significant main effects for group and time, with Group 5A consistently exhibiting the lowest mean levels. Significant group differences emerged by the 6th month. Regarding the number of cigarettes smoked, significant group differences were found, with both Group 5A and Group 3A reporting lower levels compared to the control group. Our findings add to the existing body of knowledge on the success of initiatives aimed at reducing smoking rates among young people. However, there is still a need for additional investigations in this field to further advance our understanding

Multivalent Cyclic RGD Conjugates for Targeted Delivery of Small Interfering RNA

We have designed, synthesized and tested conjugates of chemically modified luciferase siRNA (Luc-siRNA) with bi-, tri- and tetravalent cyclic(arginine-glycine-aspartic) peptides (cRGD) that selectively bind to the αvβ3 integrin. The cellular uptake, subcellular distribution and pharmacological effects of the cRGD conjugated Luc-siRNAs as compared to un-conjugated controls were examined using a luciferase reporter cassette stably transfected into αvβ3 positive M21+ human melanoma cells. The M21+ cells exhibited receptor-mediated uptake of cRGD-siRNA conjugates but not of unconjugated control siRNA. The fluorophore-tagged cRGD-siRNA conjugates were taken up by a caveolar endocytotic route and primarily accumulated in cytosolic vesicles. The bi-, tri- and tetravalent cRGD conjugates were taken up by M21+ cells to approximately the same degree. However, there were notable differences in their pharmacological effectiveness. The tri- and tetravalent versions produced progressive, dose-dependent reductions in luciferase expression, while the bivalent version had little effect. The basis for this divergence of uptake and effect is currently unclear. Nonetheless the high selectivity and substantial ‘knock down’ effects of the multivalent cRGD-siRNA conjugates suggest that this targeting and delivery strategy deserves further exploration

PREVALENCE OF RHEUMATIC HEART DISEASE AMONG SCHOOL-GOING CHILDREN IN NORTHERN AND SOUTHERN REGIONS OF SARAWAK, MALAYSIA

Rheumatic Heart Disease (RHD) is a preventable chronic heart disease caused by rheumatic fever. RHD can result in complications and can even conclude in unexpected death at a young age. This study aimed to estimate the prevalence of RHD among the school-going age group in the Northern and Southern regions of Sarawak. This research was conducted as a cross-sectional study in Samarahan and Kuching of the Southern Region and Miri of the Northern Region of Sarawak. The study population comprised school-going children within the divisions. The data on sociodemographic characteristics were collected through a questionnaire. At the same time, echocardiographic parameters were collected through a portable echocardiographic device. Cardiologists confirmed the abnormal cardiac findings. The overall prevalence of RHD was 14 per 1000 persons or 1.4%. Borderline RHD prevalence was 9 per 1000 persons or 0.9%, while the Definite RHD prevalence was 5 per 1000 persons or 0.5 %. With the prevalence obtained, more attention should be given to preventing this silent disease

Socioenvironmental Factors of Rheumatic Heart Disease among School-Going Children in Sarawak, Malaysia: A Mixed-Method Study

Socioenvironmental elements could explain the primordial and primary prevention of Rheumatic Heart Disease (RHD) in the local context. A well-planned, encompassing way to deal with RHD in the local setting is essential. Therefore, this study sought to investigate the socioenvironmental determinants of RHD among school-going children and to investigate the aetiology of RHD in the local setting. This study was conducted as a sequential explanatory mixed-methods design. A cross-sectional study was conducted in the first phase, followed by a qualitative study based on the grounded theory approach. The study was conducted in Kuching, Samarahan and Miri divisions in Sarawak among primary and secondary school-going children. The cross-sectional data collection was conducted via face-to-face interviews, while the qualitative phase was conducted via in-depth interviews. There was a preponderance of low socioeconomic status and large family size with RHD. Based on the grounded theory approach, the causes of rheumatic heart disease were classified into internal and external factors. After integrating the findings, the qualitative findings confirmed the quantitative results by confirmation and expansion without discordance. The findings would be vital for the management of RHD in terms of implementations in practice, theory, and subsequent research, as the factors were explained in the local context

Dorsal hippocampal involvement in conditioned-response timing and maintenance of temporal information in the absence of the CS

Involvement of the dorsal hippocampus (DHPC) in conditioned-response timing and maintaining temporal information across time gaps was examined in an appetitive Pavlovian conditioning task, in which rats with sham and DHPC lesions were first conditioned to a 15-s visual cue. After acquisition, the subjects received a series of non-reinforced test trials, on which the visual cue was extended (45 s) and gaps of different duration, 0.5, 2.5, and 7.5 s, interrupted the early portion of the cue. Dorsal hippocampal-lesioned subjects underestimated the target duration of 15 s and showed broader response distributions than the control subjects on the no-gap trials in the first few blocks of test, but the accuracy and precision of their timing reached the level of that of the control subjects by the last block. On the gap trials, the DHPC-lesioned subjects showed greater rightward shifts in response distributions than the control subjects. We discussed these lesion effects in terms of temporal versus non-temporal processing (response inhibition, generalisation decrement, and inhibitory conditioning)

Teaching Feedback to First-year Medical Students: Long-term Skill Retention and Accuracy of Student Self-assessment

Giving and receiving feedback are critical skills and should be taught early in the process of medical education, yet few studies discuss the effect of feedback curricula for first-year medical students. To study short-term and long-term skills and attitudes of first-year medical students after a multidisciplinary feedback curriculum. Prospective pre- vs. post-course evaluation using mixed-methods data analysis. First-year students at a public university medical school. We collected anonymous student feedback to faculty before, immediately after, and 8 months after the curriculum and classified comments by recommendation (reinforcing/corrective) and specificity (global/specific). Students also self-rated their comfort with and quality of feedback. We assessed changes in comments (skills) and self-rated abilities (attitudes) across the three time points. Across the three time points, students’ evaluation contained more corrective specific comments per evaluation [pre-curriculum mean (SD) 0.48 (0.99); post-curriculum 1.20 (1.7); year-end 0.95 (1.5); p = 0.006]. Students reported increased skill and comfort in giving and receiving feedback and at providing constructive feedback (p < 0.001). However, the number of specific comments on year-end evaluations declined [pre 3.35 (2.0); post 3.49 (2.3); year-end 2.8 (2.1)]; p = 0.008], as did students’ self-rated ability to give specific comments. Teaching feedback to early medical students resulted in improved skills of delivering corrective specific feedback and enhanced comfort with feedback. However, students’ overall ability to deliver specific feedback decreased over time

Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis

Calcium is the primary signalling component of excitation-contraction coupling, the process linking electrical excitability of cardiac muscle cells to coordinated contraction of the heart. Understanding Ca2þ handling processes at the cellular level and the role of intercellular communication in the emergence of multicellular synchronization are key aspects in the study of arrhythmias. To probe these mechanisms, we have simulated cellular interactions on large scale arrays that mimic cardiac tissue, and where individual cells are represented by a mathematical model of intracellular Ca2þ dynamics. Theoretical predictions successfully reproduced experimental findings and provide novel insights on the action of two pharmacological agents (ionomycin and verapamil) that modulate Ca2þ signalling pathways via distinct mechanisms. Computational results have demonstrated how transitions between local synchronisation events and large scale wave formation are affected by these agents. Entrainment phenomena are shown to be linked to both ntracellular Ca2þ and coupling-specific dynamics in a synergistic manner. The intrinsic variability of the cellular matrix is also shown to affect emergent patterns of rhythmicity, providing insights into the origins of arrhythmogenic Ca2þ perturbations in cardiac tissue in situ