Utilizing disease transmission and response capacities to optimize covid-19 control in Malaysia.

OBJECTIVES: Public Health Social Measures (PHSM) such as movement restriction movement needed to be adjusted accordingly during the COVID-19 pandemic to ensure low disease transmission alongside adequate health system capacities based on the COVID-19 situational matrix proposed by the World Health Organization (WHO). This paper aims to develop a mechanism to determine the COVID-19 situational matrix to adjust movement restriction intensity for the control of COVID-19 in Malaysia. METHODS: Several epidemiological indicators were selected based on the WHO PHSM interim guidance report and validated individually and in several combinations to estimate the community transmission level (CT) and health system response capacity (RC) variables. Correlation analysis between CT and RC with COVID-19 cases was performed to determine the most appropriate CT and RC variables. Subsequently, the CT and RC variables were combined to form a composite COVID-19 situational matrix (SL). The SL matrix was validated using correlation analysis with COVID-19 case trends. Subsequently, an automated web-based system that generated daily CT, RC, and SL was developed. RESULTS: CT and RC variables were estimated using case incidence and hospitalization rate; Hospital bed capacity and COVID-19 ICU occupancy respectively. The estimated CT and RC were strongly correlated [ρ = 0.806 (95% CI 0.752, 0.848); and ρ = 0.814 (95% CI 0.778, 0.839), p < 0.001] with the COVID-19 cases. The estimated SL was strongly correlated with COVID-19 cases (ρ = 0.845, p < 0.001) and responded well to the various COVID-19 case trends during the pandemic. SL changes occurred earlier during the increase of cases but slower during the decrease, indicating a conservative response. The automated web-based system developed produced daily real-time CT, RC, and SL for the COVID-19 pandemic. CONCLUSIONS: The indicators selected and combinations formed were able to generate validated daily CT and RC levels for Malaysia. Subsequently, the CT and RC levels were able to provide accurate and sensitive information for the estimation of SL which provided valuable evidence on the progression of the pandemic and movement restriction adjustment for the control of Malaysia.

Epidemiology of rumen fluke infection in selected buffalo farms in perak, malaysia: prevalence, molecular species identification, and associated risk factors.

Rumen flukes cause heavy economic losses in the ruminant industry worldwide, especially in tropical and subtropical countries. This study estimated the prevalence of rumen flukes in buffaloes, identified the species diversity, and determined risk factors associated with rumen fluke prevalence in Perak, Peninsular Malaysia. A cross-sectional study was conducted, and 321 faecal samples were collected from six buffalo farms. A structured questionnaire was developed, and farmers were interviewed to obtain information regarding risk factors associated with rumen fluke infection. The faecal samples were examined using sedimentation and Flukefinder® techniques. Genomic DNA was extracted from the fluke eggs recovered using the Flukefinder® method, and the internal transcribed spacer 2 (ITS2) fragment was amplified and sequenced to facilitate species identification. The results showed that the overall prevalence of rumen fluke across the sampled farms was 40.2% (129/321). Three rumen fluke species were identified, namely, Fischoederius elongatus, F. cobboldi, and Orthocoelium streptocoelium. Several management factors had a significant association (P < 0.05) with rumen fluke prevalence, including production type, cleaning of the stable, drinking water system, flooding around the farm, grazing system, pasture sharing with other livestock, and deworming program. This work constitutes the first attempt to understand the epidemiology of rumen fluke infection in the region and suggests that good farm management, pasture management, choosing appropriate drugs, and proper husbandry practices may improve buffalo health and production in areas where rumen flukes are prevalent.

Experiences of youth growing up with anorectal malformation or Hirschsprung's disease: a multicenter qualitative in-depth interview study.

PURPOSE: Patients with anorectal malformation (ARM) and Hirschsprung's disease (HD) live with long-term impact of these diseases even into adulthood. We aimed to explore the physical, social and emotional impact of these diseases in adolescents and young adults to develop best practices for transition care. METHODS: We conducted one-on-one in-depth interviews with ARM and HD patients aged ≥ 11 years who had undergone surgery at four tertiary referral centers. All interviews were audio-recorded and transcribed verbatim. We analyzed transcripts for recurring themes, and data were collected until data saturation was reached. Three researchers independently coded the transcripts for major themes using thematic analysis approach. RESULTS: We interviewed 16 participants (11 males) between October 2022 and April 2023. Ages ranged from 11 to 26 years. Five major themes emerged: (1) personal impact (subthemes: physical, emotional and mental health, social, school), (2) impact on family, (3) perceptions of their future (subthemes: relationships, career, state of health), (4) sources of support (subthemes: family, peers, partner), and (5) transition care (subthemes: concerns, expectations). Only females expressed concerns regarding future fertility. CONCLUSION: This study highlights the evolving problems faced by adolescents and young adults with ARM and HD, especially gender-specific concerns. Our findings can inform efforts to provide individualized care.

Morphological and molecular identification of lymnaeid snail and trematodes cercariae in different water bodies in Perak, Malaysia.

Lymnaeid snails play a crucial role in the transmission of trematode cercariae as an intermediate host that can infect humans, ruminants like buffalo, and other animals, resulting in serious economic losses. The purpose of the study was to identify the morphological and molecular characteristics of snails and cercariae collected from water bodies near buffalo farms that were integrated with palm oil in Perak, Malaysia. The presence or absence of snails in 35 water bodies was examined via cross-sectional study. From three marsh wetlands, 836 lymnaeid snails were gathered in total. Each snail's shell was morphologically identified to determine its family and species. The cercarial stage inside each snail's body was observed using the crushing method and trematode cercariae types were determined. In addition, the target gene Cytochrome c oxidase subunit 1 (Cox1) and the ribosomal internal transcribed spacer 2 (ITS2) region were used to identify the snail species and cercarial types according to the species level. The findings indicated that the collected snails belong to the family lymnaeidae and Radix rubiginosa species. In snails, the cercarial emergence infection rate was 8.7%. Echinostome, xiphidiocercariae, gymnocephalous, brevifurcate-apharyngeate distome cercariae (BADC), and longifurcate-pharyngeal monostome cercariae (LPMC) are the five morphological cercarial types that were observed. The cercariae were identified using morphological and molecular techniques, and they are members of the four families which are Echinostomatidae, Plagiorchiidae, Fasciolidae, and Schistosomatidae. Interestingly, this is the first study on R. rubiginosa and several trematode cercariae in Perak water bodies near buffalo farms that are integrated with palm oil. In conclusion, our research shown that a variety of parasitic trematodes in Perak use R. rubiginosa as an intermediate host.

Spatial prediction of soil erosion risk using knowledge-driven method in Malaysia's Steepland Agriculture Forested Valley.

Soil is a fundamental resource with its value vital to the world's ecosystem. Due to the fact that soil is one of the bases of all terrestrial life, humans cannot survive without it. However, soil erosion has jeopardized soil sustainability and affected the environmental quality, leaving a bad impact if these issues were not tackled at an earlier phase. Many research has been done to predict soil erosion susceptibility areas using different methods. This research aims to classify the contributing factors of soil erosion according to the risk and generate a soil erosion risk prediction map in Cameron Highlands. Thus, this research focuses on a knowledge-driven method that uses Analytical Hierarchy Process (AHP) technique to achieve the objectives. This technique consists of weighing the factors adopted by comparing pairs of factors that control erosion in this area through experts' opinions. 15 factors have been chosen to build the prediction map. Result shows that rainfall erosivity is the main factor contributing to soil erosion in Cameron Highlands which is 0.110, followed by land use (0.095), slope steepness (0.089), soil texture (0.079), NDVI (0.079), TWI (0.072), slope length (0.065), slope aspect (0.064), slope altitude (0.062), SPI (0.061), lithology (0.060), slope curvature (0.054), drainage density (0.049), distance to road (0.029) and distance to stream (0.025). The west part of the study area was exposed to a high risk of soil erosion. This research will give the decision-makers, policymakers and planners insight into minimizing the soil erosion problem and suggest better precautions and solutions to overcome this severe environmental problem in the more advanced phase.

Sero-prevalence of malaria and the knowledge, attitudes and practices relating to the prevention of malaria among indigenous people living in the central forest spine in Peninsular Malaysia: a mixed-methods study.

BACKGROUND: Malaria is still a major public health threat in some parts of the world. Many countries are targeting to achieve malaria free status country. This study aimed to determine the sero-prevalence of malaria and the knowledge, attitudes and practices relating to the prevention of malaria among the indigenous adults living in the central forest spine in Peninsular Malaysia. METHODS: A mixed method study was conducted in indigenous settlements in 2020. Blood film for malaria parasite (BFMP) was used to diagnose malaria in this study. A structured questionnaire was used to collect data from the participants. For the qualitative data, in-depth interviews were conducted and data was collected until data saturation was reached. Multiple linear regression was used to determine the predictors after adjusting for confounders. A p-value of < 0.05 is considered as statistically significant. Meaningful statements from the in-depth interviews were assigned to the relevant codes using NVivo version 12 software. RESULTS: A total of 284 indigenous people participated in the study. The prevalence of malaria in this study was 0%. Those in the middle age group between 25 and 41 years and tested positive for malaria previously were significantly more likely to have better knowledge and attitude scores. Significant correlations were also observed between knowledge-attitude and knowledge-practice. For the qualitative results, most of the respondents were unsure of monkey malaria, but all were aware of human malaria. CONCLUSION: The present study highlighted the absence of malaria in the study population and relatively good knowledge, attitudes and practices relating to the prevention of malaria.

Shiga toxin sub-type 2a increases the efficiency of Escherichia coli O157 transmission between animals and restricts epithelial regeneration in bovine enteroids.

Specific Escherichia coli isolates lysogenised with prophages that express Shiga toxin (Stx) can be a threat to human health, with cattle being an important natural reservoir. In many countries the most severe pathology is associated with enterohaemorrhagic E. coli (EHEC) serogroups that express Stx subtype 2a. In the United Kingdom, phage type (PT) 21/28 O157 strains have emerged as the predominant cause of life-threatening EHEC infections and this phage type commonly encodes both Stx2a and Stx2c toxin types. PT21/28 is also epidemiologically linked to super-shedding (>103 cfu/g of faeces) which is significant for inter-animal transmission and human infection as demonstrated using modelling studies. We demonstrate that Stx2a is the main toxin produced by stx2a+/stx2c+ PT21/28 strains induced with mitomycin C and this is associated with more rapid induction of gene expression from the Stx2a-encoding prophage compared to that from the Stx2c-encoding prophage. Bacterial supernatants containing either Stx2a and/or Stx2c were demonstrated to restrict growth of bovine gastrointestinal organoids with no restriction when toxin production was not induced or prevented by mutation. Isogenic strains that differed in their capacity to produce Stx2a were selected for experimental oral colonisation of calves to assess the significance of Stx2a for both super-shedding and transmission between animals. Restoration of Stx2a expression in a PT21/28 background significantly increased animal-to-animal transmission and the number of sentinel animals that became super-shedders. We propose that while both Stx2a and Stx2c can restrict regeneration of the epithelium, it is the relatively rapid and higher levels of Stx2a induction, compared to Stx2c, that have contributed to the successful emergence of Stx2a+ E. coli isolates in cattle in the last 40 years. We propose a model in which Stx2a enhances E. coli O157 colonisation of in-contact animals by restricting regeneration and turnover of the colonised gastrointestinal epithelium.

Fragment-based lead discovery of indazole-based compounds as AXL kinase inhibitors.

AXL is a member of the TAM (TYRO3, AXL, MER) subfamily of receptor tyrosine kinases. It is upregulated in a variety of cancers and its overexpression is associated with poor disease prognosis and acquired drug resistance. Utilizing a fragment-based lead discovery approach, a new indazole-based AXL inhibitor was obtained. The indazole fragment hit 11, identified through a high concentration biochemical screen, was expeditiously improved to fragment 24 by screening our in-house expanded library of fragments (ELF) collection. Subsequent fragment optimization guided by docking studies provided potent inhibitor 54 with moderate exposure levels in mice. X-ray crystal structure of analog 50 complexed with the I650M mutated kinase domain of Mer revealed the key binding interactions for the scaffold. The good potency coupled with reasonable kinase selectivity, moderate in vivo exposure levels, and availability of structural information for the series makes it a suitable starting point for further optimization efforts.

Binaural Modelling and Spatial Auditory Cue Analysis of 3D-Printed Ears.

In this work, a binaural model resembling the human auditory system was built using a pair of three-dimensional (3D)-printed ears to localize a sound source in both vertical and horizontal directions. An analysis on the proposed model was firstly conducted to study the correlations between the spatial auditory cues and the 3D polar coordinate of the source. Apart from the estimation techniques via interaural and spectral cues, the property from the combined direct and reverberant energy decay curve is also introduced as part of the localization strategy. The preliminary analysis reveals that the latter provides a much more accurate distance estimation when compared to approximations via sound pressure level approach, but is alone not sufficient to disambiguate the front-rear confusions. For vertical localization, it is also shown that the elevation angle can be robustly encoded through the spectral notches. By analysing the strengths and shortcomings of each estimation method, a new algorithm is formulated to localize the sound source which is also further improved by cross-correlating the interaural and spectral cues. The proposed technique has been validated via a series of experiments where the sound source was randomly placed at 30 different locations in an outdoor environment up to a distance of 19 m. Based on the experimental and numerical evaluations, the localization performance has been significantly improved with an average error of 0.5 m from the distance estimation and a considerable reduction of total ambiguous points to 3.3%.

Offretite Zeolite Single Crystals Synthesized by Amphiphile-Templating Approach.

Offretite zeolite synthesis in the presence of cetyltrimethylammonium bromide (CTABr) is reported. The offretite crystals were synthesized with a high crystallinity and hexagonal prismatic shape after only 72 h of hydrothermal treatment at 180 °C. The CTABr has dual-functions during the crystallization of offretite, viz. as structure-directing agent and as mesoporogen. The resulting offretite crystals, with a Si/Al ratio of 4.1, possess more acid sites than the conventional offretite due to their high crystallinity and hierarchical structure. The synthesized offretite is also more reactive than its conventional counterpart in the acylation of 2-methylfuran for biofuel production under non-microwave instant heating condition, giving 83.5% conversion with 100% selectivity to the desired product 2-acetyl-5-methylfuran. Hence, this amphiphile synthesis approach offers another cost-effective and alternative route for crystallizing zeolite materials that require expensive organic templates.

Betaine attenuates pathology by stimulating lipid oxidation in liver and regulating phospholipid metabolism in brain of methionine-choline-deficient rats.

Methyl-donor deficiency is a risk factor for neurodegenerative diseases. Dietary deficiency of the methyl-donors methionine and choline [methionine-choline-deficient (MCD) diet] is a well-established model of nonalcoholic steatohepatitis (NASH), yet brain metabolism has not been studied in this model. We hypothesized that supplemental betaine would protect both the liver and brain in this model and that any benefit to the brain would be due to improved liver metabolism because betaine is a methyl-donor in liver methylation but is not metabolically active in the brain. We fed male Sprague-Dawley rats a control diet, MCD diet, or betaine-supplemented MCD (MCD+B) diet for 8 wk and collected blood and tissue. As expected, betaine prevented MCD diet-induced NASH. However, contrary to our prediction, it did not appear to do so by stimulating methylation; the MCD+B diet worsened hyperhomocysteinemia and depressed liver methylation potential 8-fold compared with the MCD diet. Instead, it significantly increased the expression of genes involved in ß-oxidation: fibroblast growth factor 21 and peroxisome proliferator-activated receptor α. In contrast to that of the liver, brain methylation potential was unaffected by diet. Nevertheless, several phospholipid (PL) subclasses involved in stabilizing brain membranes were decreased by the MCD diet, and these improved modestly with betaine. The protective effect of betaine is likely due to the stimulation of ß-oxidation in liver and the effects on PL metabolism in brain.-Abu Ahmad, N., Raizman, M., Weizmann, N., Wasek, B., Arning, E., Bottiglieri, T., Tirosh, O., Troen, A. M. Betaine attenuates pathology by stimulating lipid oxidation in liver and regulating phospholipid metabolism in brain of methionine-choline-deficient rats.

Robust H∞-Fuzzy Logic Control for Enhanced Tracking Performance of a Wheeled Mobile Robot in the Presence of Uncertain Nonlinear Perturbations.

Motion control involving DC motors requires a closed-loop system with a suitable compensator if tracking performance with high precision is desired. In the case where structural model errors of the motors are more dominating than the effects from noise disturbances, accurate system modelling will be a considerable aid in synthesizing the compensator. The focus of this paper is on enhancing the tracking performance of a wheeled mobile robot (WMR), which is driven by two DC motors that are subject to model parametric uncertainties and uncertain deadzones. For the system at hand, the uncertain nonlinear perturbations are greatly induced by the time-varying power supply, followed by behaviour of motion and speed. In this work, the system is firstly modelled, where correlations between the model parameters and different input datasets as well as voltage supply are obtained via polynomial regressions. A robust H ∞ -fuzzy logic approach is then proposed to treat the issues due to the aforementioned perturbations. Via the proposed strategy, the H ∞ controller and the fuzzy logic (FL) compensator work in tandem to ensure the control law is robust against the model uncertainties. The proposed technique was validated via several real-time experiments, which showed that the speed and path tracking performance can be considerably enhanced when compared with the results via the H ∞ controller alone, and the H ∞ with the FL compensator, but without the presence of the robust control law.

Multi stakeholders of health and industries perspectives on medicine price transparency initiative in private health care settings in Malaysia.

INTRODUCTION: Medicine price transparency initiatives provide public or government on information about the product's prices and the components that may influence the prices, such as volume and product quality. In Malaysia, medicine price transparency has become part of the government's strategies in ensuring adequate, continuous and equitable access to quality, safe, effective and affordable medicines. Since the effect of medicine price transparency depend critically on how prices are presented, this study aims to evaluate the stakeholders' perspective of medicine price transparency practice in the private healthcare system in Malaysia. METHODS: This study was conducted as face-to-face, semi-structured interview. Respondents from private pharmaceutical industries, community pharmacists, general practitioners, private hospital pharmacists, governments, academicians and senior pharmacist were recruited using purposive sampling. Using phenomenological study approach, interviews were conducted, and audio recorded with their consent. Data were transcribed verbatim and analysed using thematic analysis with Atlas.ti 8 software and categorised as strengths, weaknesses, opportunities and threats (SWOT). RESULTS: A total of 28 respondents were interviewed. There was a mixed perception regarding the price transparency implementation in Malaysia's private healthcare settings. The potential strengths include it will provide price standardization, reduce price manipulation and competition, hence allowing the industry players to focus more on patient-care services. Moreover, the private stakeholders were concerned that the practice may affect stakeholders' business and marketing strategy, reduce profit margin, increase general practitioner's consultation fees and causing impact on geographical discrepancies. The practice was viewed as an opportunity to disseminate the truth price information to consumer and strengthen collaboration between healthcare industries and Ministry of Health although this may become a threat that affect the business survival. CONCLUSION: Price transparency initiatives would benefit the pharmaceutical industries, consumer and countries, but it needs to be implemented appropriately to prevent price manipulation, market monopoly, and business closure. Future study may want to evaluate the impact of the initiatives on the business in the industry.

Self-Adaptive Filtering Approach for Improved Indoor Localization of a Mobile Node with Zigbee-Based RSSI and Odometry.

This study presents a new technique to improve the indoor localization of a mobile node by utilizing a Zigbee-based received-signal-strength indicator (RSSI) and odometry. As both methods suffer from their own limitations, this work contributes to a novel methodological framework in which coordinates of the mobile node can more accurately be predicted by improving the path-loss propagation model and optimizing the weighting parameter for each localization technique via a convex search. A self-adaptive filtering approach is also proposed which autonomously optimizes the weighting parameter during the target node's translational and rotational motions, thus resulting in an efficient localization scheme with less computational effort. Several real-time experiments consisting of four different trajectories with different number of straight paths and curves were carried out to validate the proposed methods. Both temporal and spatial analyses demonstrate that when odometry data and RSSI values are available, the proposed methods provide significant improvements on localization performance over existing approaches.

Flex Sensor Compensator via Hammerstein-Wiener Modeling Approach for Improved Dynamic Goniometry and Constrained Control of a Bionic Hand.

In this paper, a new control-centric approach is introduced to model the characteristics of flex sensors on a goniometric glove, which is designed to capture the user hand gesture that can be used to wirelessly control a bionic hand. The main technique employs the inverse dynamic model strategy along with a black-box identification for the compensator design, which is aimed to provide an approximate linear mapping between the raw sensor output and the dynamic finger goniometry. To smoothly recover the goniometry on the bionic hand's side during the wireless transmission, the compensator is restructured into a Hammerstein-Wiener model, which consists of a linear dynamic system and two static nonlinearities. A series of real-time experiments involving several hand gestures have been conducted to analyze the performance of the proposed method. The associated temporal and spatial gesture data from both the glove and the bionic hand are recorded, and the performance is evaluated in terms of the integral of absolute error between the glove's and the bionic hand's dynamic goniometry. The proposed method is also compared with the raw sensor data, which has been preliminarily calibrated with the finger goniometry, and the Wiener model, which is based on the initial inverse dynamic design strategy. Experimental results with several trials for each gesture show that a great improvement is obtained via the Hammerstein-Wiener compensator approach where the resulting average errors are significantly smaller than the other two methods. This concludes that the proposed strategy can remarkably improve the dynamic goniometry of the glove, and thus provides a smooth human-robot collaboration with the bionic hand.

A Kinetic Approach of DPPH Free Radical Assay of Ferulate-Based Protic Ionic Liquids (PILs).

The antiradical efficiency (AE) and kinetic behavior of a new ferulate-based protic ionic liquids (PILs) were described using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay. The reduction of the DPPH free radical (DPPH•) was investigated by measuring the decrease in absorbance at 517 nm. The time to reach steady state for the reaction of parent acid (ferulic acid) and synthesized PILs with DPPH• was continuously recorded for 1 h. Results revealed that the AE of 2-butylaminoethanol ferulate (2BAEF), 3-dimethylaminopropanol ferulate (3DMAPF) and 3-diethylaminopropanol ferulate (3DEAPF) PILs have improved compared to ferulic acid (FA) as the reaction class changes from low to medium. This attributed to the strong hydrogen abstraction occurred in the PILs. Furthermore, these PILs were found to have a good kinetic behavior compared to FA due to the high rate constant (k2) (164.17, 242.84 and 244.73 M-1 s-1, respectively). The alkyl chain length and more alkyl substituents on the nitrogen atom of cation were believed to reduce the cation-anion interaction and speed up the hydrogen atom transfer (HAT) and electron transfer (ET) mechanisms; hence, increased rate constant was observed leading to a strong antioxidant activity of the synthesized PILs.

Biophysical Studies of Bacterial Topoisomerases Substantiate Their Binding Modes to an Inhibitor.

Bacterial DNA topoisomerases are essential for bacterial growth and are attractive, important targets for developing antibacterial drugs. Consequently, different potent inhibitors that target bacterial topoisomerases have been developed. However, the development of potent broad-spectrum inhibitors against both Gram-positive (G(+)) and Gram-negative (G(-)) bacteria has proven challenging. In this study, we carried out biophysical studies to better understand the molecular interactions between a potent bis-pyridylurea inhibitor and the active domains of the E-subunits of topoisomerase IV (ParE) from a G(+) strain (Streptococcus pneumoniae (sParE)) and a G(-) strain (Pseudomonas aeruginosa (pParE)). NMR results demonstrated that the inhibitor forms a tight complex with ParEs and the resulting complexes adopt structural conformations similar to those observed for free ParEs in solution. Further chemical-shift perturbation experiments and NOE analyses indicated that there are four regions in ParE that are important for inhibitor binding, namely, α2, the loop between ß2 and α3, and the ß2 and ß6 strands. Surface plasmon resonance showed that this inhibitor binds to sParE with a higher KD than pParE. Point mutations in α2 of ParE, such as A52S (sParE), affected its binding affinity with the inhibitor. Taken together, these results provide a better understanding of the development of broad-spectrum antibacterial agents.

Chaetomium globosum Cutaneous Fungal Infection Confirmed by Molecular Identification: A Case Report from Malaysia.

An 11-year-old girl presented with multiple blisters on her the right foot complicated with cellulitis. The conventional and molecular identification were performed on the culture. The internal transcribed spacer (ITS) region in rRNA gene of the isolate was amplified by PCR. The sequence of the amplified ITS region matched 99 % with that of Chaetomium globosum in the GenBank. This is the first report describing C. globosum causing cutaneous infection in Malaysia.