Parental affordability and willingness to pay for universal masking amongst government school students in Kuching, Sarawak.

INTRODUCTION: Financial affordability to purchase commodities for disease prevention is an important public health issue. The objective of this paper is to report the financial affordability and willingness to pay amongst the parents of government students for their children's nonmedical mask use, using a newly created Household Face Mask Affordability Questionnaire (MAQ). MATERIALS AND METHODS: This was a cross-sectional study involving the parents or guardians of 50.6% (44/87) government schools in the whole of Kuching Division of Sarawak. The sampling method was multistage cluster sampling, whereby stage one involved random sampling of 49.2% (30/61) primary schools and 53.8% (14/46) secondary schools in the Kuching Division, followed by stage two cluster sampling of one class per non-examination standard in each randomly sampled school. All students in the sampled classes were asked to bring a face-validated questionnaire (MAQ) back home to be answered by one of their parents or a guardian. A total of 2559 out of 3661 distributed questionnaires were collected, with a response rate of 70%. The data collection period was between April and June of 2022 so as the recall bias of the information collected, especially on the actual spending on the face masks for the school going students, was minimised. The relevant summary statistics for self-perceived face masks characteristics, face mask expenses, affordability and willingness to pay were calculated. We regress separately the monthly affordability and willingness to pay amount against age, occupation, marital status, total number of children, monthly income and monthly saving to build predictive models for affordability and willingness to pay amount per child per month. RESULTS: The average Scale-level Face Validity Indexes for all aspects of validity (clarity, comprehension, relevancy, representativeness) are high (0.91 to 1.00) for MAQ. Most of the respondents were mothers, married, working as private employees with a mean age of 41 and belonged to the B40 and M40 group. The average monthly saving per family was RM540, which was about 15% of the total income. The average actual monthly spending to purchase face masks for one child is RM24. On average, a family can afford to pay RM23.80 for one child per month to purchase face masks. The willingness to pay for the same was RM25.27. The median affordability, willingness to pay and actual spending for face masks per child was RM16.67 per month. Taking 75th percentile as the reasonable maximum expenses per child for face masks per month, the affordable amount by most parents is RM30, with the willingness to pay at 10% higher. Affordability to purchase a face mask is influenced by the marital status, occupation, income, saving and the number of dependent of the breadwinner of a household. The most important face mask characteristics expected by the parents are better filtration efficiency and easier breathability. CONCLUSION: The affordability and willingness to pay the amount to purchase face masks amongst parents of government students in Sarawak were RM30 and RM33 per child per month, respectively.

Fluctuation of BCR-ABL1 qPCRIS level beyond 0.1%IS after stopping tyrosine kinase inhibitor in chronic myeloid leukaemia patients with deep molecular response for at least two years.

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS) level below major molecular response (MMR) (0.1%IS) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion - loss of MMR for one reading - aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR.

The epidemiology of chronic myeloid leukaemia in southern Sarawak, Borneo Island.

OBJECTIVES: There are very few published chronic myeloid leukaemia (CML) epidemiology studies in South-East Asia and no representative from Malaysia. METHODS: This is a cross-sectional study of adult CML patients (citizen) in a single but representative centre in southern Sarawak. RESULTS: Total 79 patients (Malay 39%, Chinese 30.4%, Iban 17.7%, Bidayuh 12.7%) were identified from the databases. Median age at diagnosis was younger, 40, compared to developed countries due to population structure. M:F ratio was higher, 2.6:1 compared to other countries 1.3-1.7:1. Majority presented at chronic phase (89.5%), low/intermediate risk score (80%) and started imatinib (96%) as first line tyrosine kinase inhibitor (TKI), which 40% of them switched to other TKI due to intolerance (17%) and failure (including disease progression)/not achieving major molecular response (83%). Quantitative polymerase chain reaction (qPCR) assessment after three months of TKI treatment had higher positive predictive value to predict Imatinib failure, 75%, than qPCR assessment after six months of TKI treatment, 58%. Presenting phase, symptoms, signs and laboratory data were like most countries. Estimated prevalence and incidence of CML in southern Sarawak was 69.2/1,000,000 population at the Year 2016 (similar to most developing countries) and 8.0/1,000,000 population per year at the Year 2011-2016 (similar to most countries), respectively. The incidence increased with age and was lowest among Iban, 12.8 and highest among Chinese, 19.5, which was 4x higher than Chinese in China. The prevalence of different BCR-ABL1 transcript type was like other Asia countries CONCLUSION: Significant epidemiological differences on M:F ratio and ethnic groups compared to other countries warrant further study.

Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer.

Use of simulated annealing for the design of multiple repetition time balanced steady-state free precession imaging.

Balanced steady-state free precession is an ultrafast sequence with high signal-to-noise efficiency, but it also generates a strong fat signal which can mask important features. One method of fat suppression is to modify the balanced steady-state free precession spectrum using multiple repetition times to create a wide stopband over the fat frequency. However, with three or more pulse repetition times, the number of parameters creates a vast search space with many local minima of a cost function. We report on the initial results of using simulated annealing to find optimal sequences for two applications of multiple-pulse repetition time balanced steady-state free precession: positive contrast imaging and fat suppression.

Single shot concentric shells trajectories for ultra fast fMRI.

MR-encephalography is a technique that allows real-time observation of functional changes in the brain with a time-resolution of 100 ms. The high sampling rate is enabled by the use of undersampled image acquisition with regularized reconstruction. The article describes a novel imaging method for fast three-dimensional-MR-encephalography whole brain coverage based on undersampled, single-shot concentric shells trajectories and the use of multiple small receiver coils. The technique allows the observation of changes in blood oxygenation level dependent signal as a measure of brain physiology at very high temporal resolution.

Combined prospective and retrospective motion correction to relax navigator requirements.

Prospective motion correction can prevent motion artifacts in magnetic resonance imaging of the brain. However, for high-resolution imaging, the technique relies on precise tracking of head motion. This precision is often limited by tracking noise, which leads to residual errors in the prospectively-corrected k-space data and artifacts in the image. This work shows that it is possible to estimate these tracking errors, and hence the true k-space sample locations, by applying a two-sided filter to the tracking data after imaging. A conjugate gradient reconstruction is compared to gridding as a means of using this information to retrospectively correct for the effects of the residual errors.

Three-dimensional MR-encephalography: fast volumetric brain imaging using rosette trajectories.

MR-Encephalography (MREG) is a technique that allows real time observation of functional changes in the brain that appears within 100 msec. The high sampling rate is achieved at the cost of some spatial resolution. The article describes a novel imaging method for fast three-dimensional-MR-encephalography whole brain coverage based on rosette trajectories and the use of multiple small receiver coils. The technique allows the observation of changes in brain physiology at very high temporal resolution. A highly undersampled three-dimensional rosette trajectory is chosen, to perform single shot acquisition of k-space data within 23 msec. By using a 32-channel head coil array and regularized nonuniform Fourier transformation reconstruction, the spatial resolution is sufficient to detect even subtle centers of activation (e.g. human MT+). The method was applied to visual block design paradigms and compared with echo planar imaging-based functional MRI. As a proof-of-principle of the method's ability to detect local differences in the hemodynamic response functions, the analyzed MR-encephalography data revealed a spatially dependent delay of the arrival of the blood oxygenation level dependent response within the visual cortex.

Bioactivity of medicinal plant extracts against human fungal pathogens and evaluation of toxicity using Vero cells.

Medicinal plants are a potential source of new antifungal agents to combat the development of drug-resistant fungi. This study aims to investigate the aerial parts of Alternanthera sessilis (Amaranthaceae) and Ipomoea aquatica (Convolvulaceae), and the leaves of Catunaregam spinosa (Rubiaceae) and Tradescantia spathacea (Commelinaceae) for antifungal activity and cytotoxicity. The plant materials were extracted sequentially using hexane, chloroform, ethyl acetate, ethanol, methanol, and distilled water. The antifungal activity was evaluated against four species of yeasts and two species of filamentous fungi using a colorimetric broth microdilution method. The toxicity of the extracts was assessed using African monkey kidney epithelial (Vero) cells. All 24 extracts from the four medicinal plants showed inhibitory activity against all fungal species, except Aspergillus fumigatus, with a minimum inhibitory concentration range of 0.04-2.50 mg/mL. The antifungal activity of these plants was more prominent on the yeasts than the filamentous fungi. Generally, the less polar extracts (hexane, chloroform, and ethyl acetate) of the plants had stronger antifungal activity than the more polar extracts (ethanol, methanol, and water). In contrast, toxicity assessment revealed that the less polar extracts showed relatively higher toxicity towards the Vero cells than the more polar extracts. The lowest median cytotoxic concentration was shown by the chloroform extract of A. sessilis (17.4 ± 0.4 µg/mL). All water extracts, the methanol extract of I. aquatica, and the ethyl acetate, ethanol, and methanol extracts of T. spathacea did not show significant toxicity (P>0.05) towards the Vero cells. The results suggested that Tradescantia spathacea has the most promising potential for pharmaceutical developments due to its broad spectrum and selective activity against human fungal pathogens.

Multiplex RARE: a simultaneous multislice spin-echo sequence that fulfils CPMG conditions.

This work presents a new imaging sequence in which multiple slices are simultaneously excited and refocused in a spin-echo train. The multiple spin-echo trains are interleaved in such a manner that (i) the Carr-Purcell-Meiboom-Gill conditions are fulfilled at all times, and (ii) the signals from slices can be separated, preventing aliasing. This paper also demonstrates how the sequence may be used in a novel fat-water Dixon method that enables fast volume coverage. The technique is demonstrated in phantoms and in vivo.

Compressed sensing in hyperpolarized 3He lung MRI.

In this work, the application of compressed sensing techniques to the acquisition and reconstruction of hyperpolarized (3)He lung MR images was investigated. The sparsity of (3)He lung images in the wavelet domain was investigated through simulations based on fully sampled Cartesian two-dimensional and three-dimensional (3)He lung ventilation images, and the k-spaces of 2D and 3D images were undersampled randomly and reconstructed by minimizing the L1 norm. The simulation results show that temporal resolution can be readily improved by a factor of 2 for two-dimensional and 4 to 5 for three-dimensional ventilation imaging with (3)He with the levels of signal to noise ratio (SNR) (approximately 19) typically obtained. The feasibility of producing accurate functional apparent diffusion coefficient (ADC) maps from undersampled data acquired with fewer radiofrequency pulses was also demonstrated, with the preservation of quantitative information (mean ADC(cs) approximately mean ADC(full) approximately 0.16 cm(2) sec(-1)). Prospective acquisition of 2-fold undersampled two-dimensional (3)He images with a compressed sensing k-space pattern was then demonstrated in a healthy volunteer, and the results were compared to the equivalent fully sampled images (SNR(cs) = 34, SNR(full) = 19).

Multimodal assessments of Zika virus immune pathophysiological responses in marmosets.

Animal models that recapitulate the human pathophysiology have been developed as useful research tools. Although laboratory mice are widely used, they are phylogenetically "distant" to humans. New world monkeys, such as the common marmoset (Callithrix jacchus) have steadily gained prominence. In this report, marmosets are explored as an alternate in vivo model to investigate infection and immunity of Zika virus (ZIKV). Multimodal platforms, including ultrasound and magnetic resonance imaging (MRI), flow cytometry, and multiplex microbead immunoassays were established to comprehensively decipher immune responses and pathophysiological outcomes. While ZIKV-infected marmosets had detectable ZIKV RNA load in various body fluids, animals did not develop any observable lesions in their testes and brains as shown by ultrasound and MRI. Immune-phenotyping detected differences in the numbers of B cells, CD8+ T cells and HLADR+ NK cells during the first two weeks of infection. Neutralizing ZIKV-specific antibodies were elicited to high levels and targeted epitopes in the E protein. This study presents a one-stop-shop platform to study infection and pathophysiology in marmosets. While marmoset-specific research tools are being refined, the research values of these animals present them as a good model for immune-based therapies.

Treatment of murine lupus with cDNA encoding IFN-gammaR/Fc.

IFN-gamma, a pleiotropic cytokine, is a key effector molecule in the pathogenesis of several autoimmune diseases, including lupus. Importantly, deletion of IFN-gamma or IFN-gammaR in several lupus-predisposed mouse strains resulted in significant disease reduction, suggesting the potential for therapeutic intervention. We evaluated whether intramuscular injections of plasmids with cDNA encoding IFN-gammaR/Fc can retard lupus development and progression in MRL-Fas(lpr) mice. Therapy significantly reduced serum levels of IFN-gamma, as well as disease manifestations (autoantibodies, lymphoid hyperplasia, glomerulonephritis, mortality), when treatment was initiated at the predisease stage, particularly when IFN-gammaR/Fc expression was enhanced by electroporation at the injection site. Remarkably, disease was arrested and even ameliorated when this treatment was initiated at an advanced stage. This therapy represents a rare example of disease reversal and makes application of this nonviral gene therapy in humans with lupus (and perhaps other autoimmune/inflammatory conditions) highly promising.

General parameter relations for the Shinnar-Le Roux pulse design algorithm.

The magnetization ripple amplitudes from a pulse designed by the Shinnar-Le Roux algorithm are a non-linear function of the Shinnar-Le Roux A and B polynomial ripples. In this paper, the method of Pauly et al. [J. Pauly, P. Le Roux, D. Nishimura, A. Macovski, Parameter relations for the Shinnar-Le Roux selective excitation pulse design algorithm, IEEE Transactions on Medical Imaging 10 (1991) 56-65.] has been extended to derive more general parameter relations. These relations can be used for cases outside the five classes considered by Pauly et al., in particular excitation pulses for flip angles that are not small or 90 degrees. Use of the new relations, together with an iterative procedure to obtain polynomials with the specified ripples from the Parks-McClellan algorithm, are shown to give simulated slice profiles that have the desired ripple amplitudes.

SNR phase order k-space encoding (SPOKE).

A method of determining the phase-encode order for MR Fourier-encoded imaging is described, which provides an additional option for optimizing images from samples with signals that change during data acquisition. Examples are in hyperpolarized helium gas imaging of the lungs where polarization is lost with each RF pulse or the signal changes observed in rapid dynamic studies with T(1) or T(2)* contrast agents when mixing is taking place. The method uses a single frequency-encoded projection in the proposed phase-encoding direction. The projection is subsequently sorted into signal-to-noise ratio (SNR) order. The indices of the sorted array are then used to create the phase-encode table to be used for the scan. This phase table is sorted in descending SNR order for signals that decrease during data acquisition and in ascending order for signals that increase during data acquisition. Simulations suggest that this technique can produce higher resolution than centric-ordered phase encoding at the expense of increased modulation (ghosting) artifact for dynamically changing signals. Initial practical implementation of the technique has been carried out on a dedicated 0.2-T Niche MR system, and the test object results agree well with simulations. Hyperpolarized 3-He lung images have also been acquired and postprocessed using the SNR phase order k-space encoding (SPOKE) methodology and show potential for improved imaging with high flip angles where polarization is rapidly lost. Applications may also be found for 3D volumetric acquisitions where two dimensions can be SPOKE encoded.

The fission yeast DNA structure checkpoint protein Rad26ATRIP/LCD1/UVSD accumulates in the cytoplasm following microtubule destabilization.

BACKGROUND: DNA structure checkpoints are conserved eukaryotic signal transduction pathways that help preserve genomic integrity. Upon detecting checkpoint signals such as stalled replication forks or double-stranded DNA breaks, these pathways coordinate appropriate stress responses. Members of the PI-3 kinase related kinase (PIKK) family are essential elements of DNA structure checkpoints. In fission yeast, the Rad3 PIKK and its regulatory subunit Rad26 coordinate the detection of checkpoint signals with pathway outputs. RESULTS: We found that untreated rad26Delta cells were defective for two microtubule-dependent processes: chromosome segregation and morphogenesis. Interestingly, cytoplasmic accumulation of Rad26-GFP occurred following treatment with microtubule destabilizing drugs, but not during treatment with the genotoxic agent Phleomycin. Cytoplasmic accumulation of Rad26-GFP depended on Rad24, a 14-3-3 protein also required for DNA structure checkpoints and morphogenesis. Results of over expression and epistasis experiments confirm that Rad26 and Rad24 define a response to microtubule destabilizing conditions. CONCLUSION: Two DNA structure checkpoint proteins with roles in morphogenesis define a response to microtubule destabilizing conditions.

Automated gamma knife radiosurgery treatment planning with image registration, data-mining, and Nelder-Mead simplex optimization.

Gamma knife treatments are usually planned manually, requiring much expertise and time. We describe a new, fully automatic method of treatment planning. The treatment volume to be planned is first compared with a database of past treatments to find volumes closely matching in size and shape. The treatment parameters of the closest matches are used as starting points for the new treatment plan. Further optimization is performed with the Nelder-Mead simplex method: the coordinates and weight of the isocenters are allowed to vary until a maximally conformal plan specific to the new treatment volume is found. The method was tested on a randomly selected set of 10 acoustic neuromas and 10 meningiomas. Typically, matching a new volume took under 30 seconds. The time for simplex optimization, on a 3 GHz Xeon processor, ranged from under a minute for small volumes (<1000 cubic mm, 2-3 isocenters), to several tens of hours for large volumes (>30,000 cubic mm, >20 isocenters). In 8/10 acoustic neuromas and 8/10 meningiomas, the automatic method found plans with conformation number equal or better than that of the manual plan. In 4/10 acoustic neuromas and 5/10 meningiomas, both overtreatment and undertreatment ratios were equal or better in automated plans. In conclusion, data-mining of past treatments can be used to derive starting parameters for treatment planning. These parameters can then be computer optimized to give good plans automatically.

Simultaneous parallel inclined readout image technique.

Sensitivity-encoded phase undersampling has been combined with simultaneous slice excitation to produce a parallel MRI method with a high volumetric acquisition acceleration factor without the need for auxiliary stepped field coils. Dual-slice excitation was produced by modulating both spin and gradient echo sequences at +/-6 kHz. Frequency aliasing of simultaneously excited slices was prevented by using an additional gradient applied along the slice axis during data acquisition. Data were acquired using a four-channel receiver array and x4 sensitivity encoding on a 1.5 T MR system. The simultaneous parallel inclined readout image technique has been successfully demonstrated in both phantoms and volunteers. A multiplicative image acquisition acceleration factor of up to x8 was achieved. Image SNR and resolution was dependent on the ratio of the readout gradient to the additional slice gradient. A ratio of approximately 2:1 produced acceptable image quality. Use of RF pulses with additional excitation bands should enable the technique to be extended to volumetric acquisition acceleration factors in the range of x16-24 without the SNR limitations of pure partially parallel phase reduction methods.

Immunochemical studies of yellowjacket venom proteins.

The major proteins of yellowjacket venoms have been isolated and characterized immuno-chemically. They consist of hyaluronidase, phospholipase, and antigen 5. Venoms from three species of yellowjacket were studied. Vespula germanica, V. maculifrons, and V. vulgaris. The phospholipases could be isolated in good yield only when affinity chromatography was used to minimize limited proteolysis. A kallikrein-like peptidase was found present in the yellowjacket venom. Phospholipases from these three species were immunochemically indistinguishable from each other, as were their antigen 5s. Sera from individuals sensitive to yellowjacket venom contained IgE and IgG specific for antigen 5 and phospholipase.

Structure-activity relationships: analogues of the dicaffeoylquinic and dicaffeoyltartaric acids as potent inhibitors of human immunodeficiency virus type 1 integrase and replication.

The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations. Since integrase is an excellent target for anti-HIV therapy, structure-activity relationships were employed to synthesize compounds with: (1) improved potency against HIV-1 integrase, (2) improved anti-HIV effect in tissue culture, and (3) increased selectivity as indicated by low cellular toxicity. Thirty-four analogues of the DCTAs and DCQAs were synthesized and tested for cell toxicity, anti-HIV activity, and inhibition of HIV-1 integrase. Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0. 07 to >10 microM. Seventeen analogues that were synthesized or purchased had no inhibitory activity against integrase at concentrations of 25 microM. Of the biologically active analogues, 7 of the 17 inhibited HIV replication at nontoxic concentrations. The most potent compounds were D-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid, digalloyl-L-tartaric acid, bis(3,4-dihydroxybenzoyl)-L-tartaric acid, dicaffeoylglyceric acid, and bis(3, 4-dihydroxyphenylacetyl)-L-tartaric acid. Anti-HIV activity of the active compounds in tissue culture ranged from 35 to 0.66 microM. Structure-activity relationships demonstrated that biscatechol moieties were absolutely required for inhibition of integrase, while at least one free carboxyl group was required for anti-HIV activity. These data demonstrate that analogues of the DCTAs and the DCQAs can be synthesized which have improved activity against HIV integrase.