Effectiveness of a pharmacist-led, community group-based education programme in enhancing diabetes management: A multicentre randomised control trial.

Aims: This study presents a protocol for the Pharmacy Integrated Community Care (PICC) program, meticulously designed to enhance Hemoglobin A1c (HbA1c) levels and augment knowledge about diabetes mellitus (DM) among individuals diagnosed with Type 2 Diabetes Mellitus (T2DM) in the Sarawak State of Malaysia. Methods: From 1 May to December 31, 2023, a prospective, multicenter, parallel-design randomised controlled trial will be conducted with two groups, each consisting of 47 participants. The intervention group will receive a structured, four-session group-based program guided by experienced pharmacists, focusing on medication adherence and diabetes management. The control group will follow the standard Diabetes Mellitus Adherence Clinic program. The primary outcomes of this study encompass enhancements in knowledge regarding diabetes medication management and adherence, followed by subsequent changes in HbA1c levels. Conclusions: The successful implementation of the PICC program holds promise for enhancing health outcomes in the T2DM population, potentially leading to more effective diabetes management initiatives and better health practices in the community. Trial registration clinicaltrialsgov identifier: NCT05106231.

Effect of cysteine mutation at Ca2+ coordinating residues to the autolysis, folding and hydrophobicity of full length and mature Rand protease: molecular dynamics simulation and essential dynamics.

Rand protease is a serine protease that shared common characteristics with members of the MEROPS S8 subtilisin family. It is thermostable, highly stable in organic solvent and broad in specificity. Many structures of homologous protein solved by X-ray crystallography and NMR have been deposited to Protein Data Bank (PDB) which allowed this study to rely on structure prediction by deep learning to build three-dimensional (3D) structure of full length and mature Rand protease (flRP and mRP). In silico cysteine mutation to 7 predicted high affinity Ca2+ coordinating residues were introduced, and the mutants were subjected to molecular dynamics simulation to study its effect on flRP and mRP. MD simulation showed a marked increase in flexibility of the pro-peptide segment indicating the impact of single cysteine substitution at high affinity Ca2+ coordinating residues to autolysis of flRP. MD simulation for mRP reaffirmed the role of Ca2+ coordinating sites in providing stability to Rand protease. In addition, these residues also affect the autolysis, folding and hydrophobicity of RP. Essential dynamics observed large contribution of the first few eigenvectors of flRP, mRP and their high affinity Ca2+ coordinating residues mutants to the TMSF values which indicates that these values account for a large portion of the overall atomic fluctuations. These results have given a more comprehensive understanding on the role of cysteine substituted Ca2+ coordinating surface loop to the structure of flRP and mRP which are important in contributing to the structural stability of subtilisin.Communicated by Ramaswamy H. Sarma.

Narrative Review of the Control and Prevention of Knowlesi Malaria.

Despite the reduction in the number of cases of human malaria throughout the world, the incidence rate of knowlesi malaria is continuing to rise, especially in Southeast Asia. The conventional strategies for the prevention and control of human malaria can provide some protection against knowlesi malaria. Despite the numerous studies on the risk factors and the innovative methods that may be used to prevent and control the vectors of Plasmodium knowlesi, the incidence rate remains high. An integrated approach that includes environmental intervention should be adopted in order to ensure the successful control of zoonotic malaria. A combination of personal-level protection, vector control and environmental control may mitigate the risk of Plasmodium knowlesi transmission from macaques to humans and, ultimately, reduce the incidence rate of knowlesi malaria.

Influence of Irradiation Time on the Structural and Optical Characteristics of CuSe Nanoparticles Synthesized via Microwave-Assisted Technique.

A rapid, sustainable, and ecologically sound approach is urgently needed for the production of semiconductor nanomaterials. CuSe nanoparticles (NPs) were synthesized via a microwave-assisted technique using CuCl2·2H2O and Na2SeO3 as the starting materials. The role of the irradiation time was considered as the primary concern to regulate the size and possibly the shape of the synthesized nanoparticles. A range of characterization techniques was used to elucidate the structural and optical properties of the fabricated nanoparticles, which included X-ray diffraction, energy-dispersive X-ray spectroscopy (EDX), atomic force microscopy, field emission scanning electron microscopy, Raman spectroscopy (Raman), UV-Visible diffuse reflectance spectroscopy (DRS), and photoluminescence spectroscopy (PL). The mean crystallite size of the CuSe hexagonal (Klockmannite) crystal structure increased from 21.35 to 99.85 nm with the increase in irradiation time. At the same time, the microstrain and dislocation density decreased from 7.90 × 10-4 to 1.560 × 10-4 and 4.68 × 10-2 to 1.00 × 10-2 nm-2, respectively. Three Raman vibrational bands attributed to CuSe NPs have been identified in the Raman spectrum. Irradiation time was also seen to play a critical role in the NP optical band gap during the synthesis. The decrease in the optical band gap from 1.85 to 1.60 eV is attributed to the increase in the crystallite size when the irradiation time was increased. At 400 nm excitation wavelength, a strong orange emission centered at 610 nm was observed from the PL measurement. The PL intensity is found to increase with an increase in irradiation time, which is attributed to the improvement in crystallinity at higher irradiation time. Therefore, the results obtained in this study could be of great benefit in the field of photonics, solar cells, and optoelectronic applications.

Adsorption of Methylene Blue Dye by Calix[6]Arene-Modified Lead Sulphide (Pbs): Optimisation Using Response Surface Methodology.

Lead sulphide (PbS) modified with calix[6]arene was synthesised as an alternative and regenerative adsorbent for the adsorption of methylene blue (MB) dye. The prepared calix[6]arene-modified PbS was characterised via Fourier-transform infrared spectroscopy, field emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The response surface methodology (RSM) based on the central composite design (CCD) was employed to identify the most significant factors, such as the initial concentration, adsorbent dosage, pH, and temperature, and to optimise the effects of the factors on the adsorptive efficiency as its response. The optimised initial concentration, adsorbent dosage, pH, and temperature were 20.00 mg/L initial concentration, 44.00 mg calix[6]arene-modified PbS, pH 6, and a temperature of 31.00 °C. A good correlation between the values and well-fitted model was observed. The adsorption performance was evaluated based on the percentage removal of MB dye from the water system. The adsorption isotherm best fit the Langmuir isotherm model, and the adsorption rate was followed by a pseudo-second-order kinetic model, a single layer chemical adsorption with a maximum adsorption capacity (qmax) of 5.495 mg/g.

Photoluminescence Investigation of Carrier Localization in Colloidal PbS and PbS/MnS Quantum Dots.

The existence of surface organic capping ligands on quantum dots (QDs) has limited the potential in QDs emission properties and energy band gap structure alteration as well as the carrier localization. This drawback can be addressed via depositing a thin layer of a semiconductor material on the surface of QDs. Herein, we report on the comparative study for photoluminescent (PL) properties of PbS and PbS/MnS QDs. The carrier localization effect due to the alteration of energy band gap structure and carrier recombination mechanism in the QDs were investigated via PL measurements in a temperature range of 10-300 K with the variation of the excitation power from 10 to 200 mW. For PbS QDs, the gradient of integrated PL intensity (IPL) as a function of excitation power density graph was less than unity. When the MnS shell layer was deposited onto the PbS core, the PL emission exhibited a blue shift, showing dominant carrier recombination. It was also found that the full width half-maximum showed a gradual broadening with the increasing temperature, affirming the electron-phonon interaction.

Diagnostic Reference Level of Radiation Dose and Image Quality among Paediatric CT Examinations in A Tertiary Hospital in Malaysia.

Pediatrics are more vulnerable to radiation and are prone to dose compared to adults, requiring more attention to computed tomography (CT) optimization. Hence, diagnostic reference levels (DRLs) have been implemented as part of optimization process in order to monitor CT dose and diagnostic quality. The noise index has recently been endorsed to be included as a part of CT optimization in the DRLs report. In this study, we have therefore set local DRLs for pediatric CT examination with a noise index as an indicator of image quality. One thousand one hundred and ninety-two (1192) paediatric patients undergoing CT brain, CT thorax and CT chest-abdomen-pelvis (CAP) examinations were analyzed retrospectively and categorized into four age groups; group 1 (0-1 year), group 2 (1-5 years), group 3 (5-10 years) and group 4 (10-15 years). For each group, data such as the volume-weighted CT dose index (CTDIvol), dose-length product (DLP) and the effective dose (E) were calculated and DRLs for each age group set at 50th percentile were determined. Both CT dose and image noise values between age groups have differed significantly with p-value < 0.05. The highest CTDIvol and DLP values in all age groups with the lowest noise index value reported in the 10-15 age group were found in CT brain examination. In conclusion, there was a significant variation in doses and noise intensity among children of different ages, and the need to change specific parameters to fit the clinical requirement.

The Role of Surface Exposed Lysine in Conformational Stability and Functional Properties of Lipase from Staphylococcus Family.

Surface charge residues have been recognized as one of the stability determinants in protein. In this study, we sought to compare and analyse the stability and conformational dynamics of staphylococcal lipase mutants with surface lysine mutation using computational and experimental methods. Three highly mutable and exposed lysine residues (Lys91, Lys177, Lys325) were targeted to generate six mutant lipases in silico. The model structures were simulated in water environment at 25 °C. Our simulations showed that the stability was compromised when Lys177 was substituted while mutation at position 91 and 325 improved the stability. To illustrate the putative alterations of enzyme stability in the stabilising mutants, we characterized single mutant K325G and double mutant K91A/K325G. Both mutants showed a 5 °C change in optimal temperature compared to their wild type. Single mutant K325G rendered a longer half-life at 25 °C (T1/2 = 21 h) while double mutant K91A/K325G retained only 40% of relative activity after 12 h incubation. The optimal pH for mutant K325G was shifted from 8 to 9 and similar substrate preference was observed for the wild type and two mutants. Our findings indicate that surface lysine mutation alters the enzymatic behaviour and, thus, rationalizes the functional effects of surface exposed lysine in conformational stability and activity of this lipase.

Evaluating the toxicity of polyurethane during marine clay stabilisation.

In civil engineering, many geotechnical and forensic projects employ polyurethane (PU) for ground improvement, and the results have shown to be effective in terms of time and cost savings. However, similar to many other chemical stabilisers, the use of PU for soil stabilisation may have environmental repercussions. Therefore, this paper utilised a toxicity characteristic leaching procedure (TCLP) to investigate the potential for ground contamination resulting from the application of PU for the stabilisation of marine clay. Furthermore, the hazardousness of PU during the stabilisation of marine clay was investigated by testing its reactivity, ignitability, corrosivity and physical properties. The results reveal that the quantity of heavy metals present in PU is far below the regulatory limits. The results further confirm that PU is odourless and non-corrosive and that it is non-cyanide and non-sulphide-bearing. However, PU is capable of igniting. Overall, the potential application of PU for ground improvement is promising due to its environmental friendliness.

Effects of Lid 1 Mutagenesis on Lid Displacement, Catalytic Performances and Thermostability of Cold-active Pseudomonas AMS8 Lipase in Toluene.

Pseudomonas fluorescens AMS8 lipase lid 1 structure is rigid and holds unclear roles due to the absence of solvent-interactions. Lid 1 region was stabilized by 17 hydrogen bond linkages and displayed lower mean hydrophobicity (0.596) compared to MIS38 lipase. Mutating lid 1 residues, Thr-52 and Gly-55 to aromatic hydrophobic-polar tyrosine would churned more side-chain interactions between lid 1 and water or toluene. This study revealed that T52Y leads G55Y and its recombinant towards achieving higher solvent-accessible surface area and longer half-life at 25 to 37 °C in 0.5% (v/v) toluene. T52Y also exhibited better substrate affinity with long-chain carbon substrate in aqueous media. The affinity for pNP palmitate, laurate and caprylate increased in 0.5% (v/v) toluene in recombinant AMS8, but the affinity in similar substrates was substantially declined in lid 1 mutated lipases. Regarding enzyme efficiency, the recombinant AMS8 lipase displayed highest value of kcat/Km in 0.5% (v/v) toluene, mainly with pNPC. In both hydrolysis reactions with 0% and 0.5% (v/v) toluene, the enzyme efficiency of G55Y was found higher than T52Y for pNPL and pNPP. At 0.5% (v/v) toluene, both mutants showed reductions in activation energy and enthalpy values as temperature increased from 25 to 35 °C, displaying better catalytic functions. Only T52Y exhibited increase in entropy values at 0.5% (v/v) toluene indicating structure stability. As a conclusion, Thr-52 and Gly-55 are important residues for lid 1 stability as their existence helps to retain the geometrical structure of alpha-helix and connecting hinge.

Directed Evolution of Recombinant C-Terminal Truncated Staphylococcus epidermidis Lipase AT2 for the Enhancement of Thermostability.

In the industrial processes, lipases are expected to operate at temperatures above 45 °C and could retain activity in organic solvents. Hence, a C-terminal truncated lipase from Staphylococcus epidermis AT2 (rT-M386) was engineered by directed evolution. A mutant with glycine-to-cysteine substitution (G210C) demonstrated a remarkable improvement of thermostability, whereby the mutation enhanced the activity five-fold when compared to the rT-M386 at 50 °C. The rT-M386 and G210C lipases were purified concurrently using GST-affinity chromatography. The biochemical and biophysical properties of both enzymes were investigated. The G210C lipase showed a higher optimum temperature (45 °C) and displayed a more prolonged half-life in the range of 40-60 °C as compared to rT-M386. Both lipases exhibited optimal activity and stability at pH 8. The G210C showed the highest stability in the presence of polar organic solvents at 50 °C compared to the rT-M386. Denatured protein analysis presented a significant change in the molecular ellipticity value above 60 °C, which verified the experimental result on the temperature and thermostability profile of G210C.

The Role of Solvent-Accessible Leu-208 of Cold-Active Pseudomonas fluorescens Strain AMS8 Lipase in Interfacial Activation, Substrate Accessibility and Low-Molecular Weight Esterification in the Presence of Toluene.

The alkaline cold-active lipase from Pseudomonas fluorescens AMS8 undergoes major structural changes when reacted with hydrophobic organic solvents. In toluene, the AMS8 lipase catalytic region is exposed by the moving hydrophobic lid 2 (Glu-148 to Gly-167). Solvent-accessible surface area analysis revealed that Leu-208, which is located next to the nucleophilic Ser-207 has a focal function in influencing substrate accessibility and flexibility of the catalytic pocket. Based on molecular dynamic simulations, it was found that Leu-208 strongly facilitates the lid 2 opening via its side-chain. The KM and Kcat/KM of L208A mutant were substrate dependent as it preferred a smaller-chain ester (pNP-caprylate) as compared to medium (pNP-laurate) or long-chain (pNP-palmitate) esters. In esterification of ethyl hexanoate, L208A promotes a higher ester conversion rate at 20 °C but not at 30 °C, as a 27% decline was observed. Interestingly, the wild-type (WT) lipase's conversion rate was found to increase with a higher temperature. WT lipase AMS8 esterification was higher in toluene as compared to L208A. Hence, the results showed that Leu-208 of AMS8 lipase plays an important role in steering a broad range of substrates into its active site region by regulating the flexibility of this region. Leu-208 is therefore predicted to be crucial for its role in interfacial activation and catalysis in toluene.

Mitragyna speciosa use in the northern states of Malaysia: a cross-sectional study.

ETHNOPHARMACOLOGICAL RELEVANCE: The consumption of Mitragyna speciosa (MS) for its psychoactive effects is widely reported amongst people in the villages in Thailand and Malaysia even though its use is illegal. AIM OF THE STUDY: This study examined the pattern of MS use, its reported effects and explored its potential to cause dependence. MATERIALS AND METHODS: We used both convenience and snowball-sampling methods to recruit participants in a border town between two northern states in Malaysia. Face-to-face interviews were conducted with the use of a structured questionnaire on 562 respondents who gave oral consent to participate in the study. RESULTS: The response rate was 91%. The majority of the respondents (88%) reported daily use of MS. The main mode of using MS was by drinking the MS extract as tea (90%). The mean age of starting MS use was 28.3 (SD=8.1) years. A variety of reasons were given for using MS including for social and recreational needs, stamina and physical endurance, pain relief and improved sexual performance. Despite its reported usefulness in weaning off opiate addiction, 460 (87%) admitted they were not able to stop using MS. Only education level had a statistically significant association with the ability to stop or not stop the use of MS (χ(2)=31.0, df=1, p<0.001). Significantly higher proportions of those with a lower education level (38%) were able to stop using MS compared to respondents with a higher education level. CONCLUSIONS: Our study provides important information on the pattern of MS use, its effects and its potential to cause addiction, as there has been growing interest in MS as evidenced by the number of advertisements for its sale on the Internet. Future study is required to explore its psychological and social impact on users.