A protocol on information-motivation-behavioural skills risk of intensive phase treatment interruption among pulmonary tuberculosis patients in urban districts, Selangor

Introduction: Despite advancement of treatment modalities, Tuberculosis (TB) treatment interruption rate has globally accelerating, calling for greater framework shifting towards psychosocial intervention. Similarly, Selangor state had reported the perturbing TB treatment interruption rate, which was figured persistently above 10% in the interval year of 2014 to 2018, thus signifies an empirical assessment on Information-Motivation-Behavioural skills (IMB) determinants of TB intensive phase treatment. This study aims to determine the time to intensive phase TB treatment interruption and its prognostic factors among newly diagnosed pulmonary Tuberculosis (PTB) smear positive patients in urban district Selangor. Methods: A multi-centric prospective cohort study will recruit 695 newly diagnosed PTB smear positive patients at treatment centres in urban districts, Selangor. This study will utilize validated self-administered questionnaire and standardised data collection form (PROFORMA). At baseline, we will elicit information on IMB models constructs, additionally on socio-demographics, health service factors and clinical characteristics. Meanwhile, four points follow up will be executed to retrieve information on treatment status and time varying effects of body weight, treatment side effects, symptoms improvement and internalised stigma. Finally, survival analysis will be computed to identify the time to intensive phase treatment interruption and its prognostic factors. Conclusion: This study will enlighten IMB model determinants of intensive phase treatment interruption, hence to endeavour psychosocial elements in designing time relevant public health strategies in TB case management

Early nutrition, growth and cognitive development of infants from birth to 2 years in Malaysia: a study protocol

Background: The first 2 years of life is a critical period of rapid growth and brain development. During this period, nutrition and environmental factors play important roles in growth and cognitive development of a child. This report describes the study protocol of early nutrition, growth and cognitive development of infants from birth to 2 years of age. Methods/Design: This is a prospective cohort study of mothers and infants recruited from government health clinics in Seremban district in Negeri Sembilan, Malaysia. Infants are followed-up at 6, 12, 18 and 24 months of age. Pre-natal factors that include mother’s pre-pregnancy body mass index, gestational weight gain, blood glucose and blood pressure during pregnancy, infant’s gestational age, birth weight and head circumference at birth are obtained from patient card. Post-natal factors assessed at each follow-up are feeding practices, dietary intake, anthropometric measurements and cognitive development of infants. Iron status is assessed at 6 months, while infant temperament and home environment are assessed at 12 months. Maternal intelligence is assessed at 18 months. Discussion: Early life nutritional programming is of current interest as many longitudinal studies are actively being conducted in developed countries to investigate this concept. The concept however is relatively new in developing countries such as Malaysia. This study will provide useful information on early nutrition and infant development in the first two years of life which can be further followed up to identify factors that track into childhood and contribute to growth and cognitive deviations

The effectiveness of educational programs on parenting stress and coping mechanism among parents of children with autism spectrum disorder: a systematic review

The aim of this systematic review was to evaluate the effectiveness of educational programs on parenting stress and coping mechanism among parents of children with Autism Spectrum Disorder. Our current review retrieved the articles from databases such as CINAHL, Springer, Ovid, PubMed, Google Scholar, and EBSCO host. Only articles published between the years of 2000 and 2018 in these databases were recruited using keywords such as Autism Spectrum Disorder, education program, parenting stress, coping mechanism, and coping strategies. The search generated 17 articles; 8 articles were relevant. This systematic review provides an important opportunity to advance our understanding of the effectiveness of the educational program for reducing parenting stress and improving coping mechanism among parents of children with Autism Spectrum Disorder. Nurses could also have a pivotal role in delivering the educational program for parents of children with ASD

Mobile based Automated Complete Blood Count (Auto-CBC) Analysis System from Blood Smeared Image

Blood cells diagnosis is becoming essential to ensure a proper treatment can be proposed to a blood related disease patient. In current research trending, automated complete blood count analysis system is required for pathologists or researchers to count the blood cells from the blood smeared images. Hence, a portable mobile-based complete blood count (CBC) analysis framework with the aid of microscope is proposed, and the smartphone camera is mounted to the viewing port of the light microscope by adding a smartphone support. Initially, the blood smeared image is acquired from a light microscope with objective zoom of 100X magnifications view the eyepiece zoom of 10X magnification, then captured by the smartphone camera. Next, the areas constitute to the WBC and RBC are extracted using combination of color space analysis, threshold and Otsu procedure. Then, the number of corresponding cells are counted using topological structural analysis, and the cells in clumped region is estimated using Hough Circle Transform (HCT) procedure. After that, the analysis results are saved in the database, and shown in the user interface of the smartphone application. Experimental results show the developed system can gain 92.93% accuracy for counting the RBC whereas 100% for counting the WBC

Fragmented QRS is independently predictive of long-term adverse clinical outcomes in Asian patients hospitalized for heart failure: A retrospective cohort study

Fragmented QRS (fQRS) results from myocardial scarring and predicts cardiovascular mortality and ventricular arrhythmia (VA). We evaluated the prevalence and prognostic value of fQRS in Asian patients hospitalized for heart failure. This was a retrospective cohort study of adult patients hospitalized for heart failure between 1st January 2010 and 31st December 2016 at a tertiary center in Hong Kong. The baseline ECG was analyzed. QRS complexes (2 contiguous leads was an independent predictor of SCD (HR 2.679 [1.252, 5.729], = 0.011). In patients without ischaemic heart disease ( = 1,396), fQRS in any leads remained predictive of VA and SCD (adjusted HR 3.526 [1.399, 8.887], = 0.008, and 1.873 [1.103, 3.181], = 0.020, respectively), but not cardiovascular mortality (adjusted HR 1.064 [0.671, 1.686], = 0.792). fQRS is an independent predictor of cardiovascular mortality, VA, and SCD. Higher fQRS burden increased SCD risk. The implications of fQRS in heart failure patients without ischaemic heart disease require further studies. [Abstract copyright: Copyright © 2021 Chan, Zhou, Lee, Li, Tan, Leung, Jeevaratnam, Liu, Roever, Liu, Tse and Zhang.

The presence of broadly neutralizing anti-SARS-CoV-2 RBD antibodies elicited by primary series and booster dose of COVID-19 vaccine

Antibody-mediated immunity plays a key role in protection against SARS-CoV-2. We characterized B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals and elucidate the mechanism of action of broadly neutralizing antibodies and dissect antibodies at the epitope level. The breadth and clonality of anti-RBD B cell response varies among individuals. The majority of neutralizing antibody clones lose or exhibit reduced activities against Beta, Delta, and Omicron variants. Nevertheless, a portion of anti-RBD antibody clones that develops after a primary series or booster dose of COVID-19 vaccination exhibit broad neutralization against emerging Omicron BA.2, BA.4, BA.5, BQ.1.1, XBB.1.5 and XBB.1.16 variants. These broadly neutralizing antibodies share genetic features including a conserved usage of the IGHV3-53 and 3–9 genes and recognize three clustered epitopes of the RBD, including epitopes that partially overlap the classically defined set identified early in the pandemic. The Fab-RBD crystal and Fab-Spike complex structures corroborate the epitope grouping of antibodies and reveal the detailed binding mode of broadly neutralizing antibodies. Structure-guided mutagenesis improves binding and neutralization potency of antibody with Omicron variants via a single amino-substitution. Together, these results provide an immunological basis for partial protection against severe COVID-19 by the ancestral strain-based vaccine and indicate guidance for next generation monoclonal antibody development and vaccine design

AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome

<p>Abstract</p> <p>Background</p> <p>To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance.</p> <p>Results</p> <p>Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA.</p> <p>Conclusions</p> <p>AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts.</p

Fragmented QRS Is Independently Predictive of Long-Term Adverse Clinical Outcomes in Asian Patients Hospitalized for Heart Failure: A Retrospective Cohort Study

Background: Fragmented QRS (fQRS) results from myocardial scarring and predicts cardiovascular mortality and ventricular arrhythmia (VA). We evaluated the prevalence and prognostic value of fQRS in Asian patients hospitalized for heart failure. Methods and Results: This was a retrospective cohort study of adult patients hospitalized for heart failure between 1st January 2010 and 31st December 2016 at a tertiary center in Hong Kong. The baseline ECG was analyzed. QRS complexes (2 contiguous leads was an independent predictor of SCD (HR 2.679 [1.252, 5.729], p = 0.011). In patients without ischaemic heart disease (N = 1,396), fQRS in any leads remained predictive of VA and SCD (adjusted HR 3.526 [1.399, 8.887], p = 0.008, and 1.873 [1.103, 3.181], p = 0.020, respectively), but not cardiovascular mortality (adjusted HR 1.064 [0.671, 1.686], p = 0.792). Conclusion: fQRS is an independent predictor of cardiovascular mortality, VA, and SCD. Higher fQRS burden increased SCD risk. The implications of fQRS in heart failure patients without ischaemic heart disease require further studies

Characterization of the commercially-available fluorescent chloroquine-BODIPY conjugate, LynxTag-CQGREEN, as a marker for chloroquine resistance and uptake in a 96-well plate assay

Chloroquine was a cheap, extremely effective drug against Plasmodium falciparum until resistance arose. One approach to reversing resistance is the inhibition of chloroquine efflux from its site of action, the parasite digestive vacuole. Chloroquine accumulation studies have traditionally relied on radiolabelled chloroquine, which poses several challenges. There is a need for development of a safe and biologically relevant substitute. We report here a commercially-available green fluorescent chloroquine-BODIPY conjugate, LynxTag-CQGREEN, as a proxy for chloroquine accumulation. This compound localized to the digestive vacuole of the parasite as observed under confocal microscopy, and inhibited growth of chloroquine-sensitive strain 3D7 more extensively than in the resistant strains 7G8 and K1. Microplate reader measurements indicated suppression of LynxTag-CQGREEN efflux after pretreatment of parasites with known reversal agents. Microsomes carrying either sensitive or resistant-type PfCRT were assayed for uptake; resistant-type PfCRT exhibited increased accumulation of LynxTag-CQGREEN, which was suppressed by pretreatment with known chemosensitizers. Eight laboratory strains and twelve clinical isolates were sequenced for PfCRT and Pgh1 haplotypes previously reported to contribute to drug resistance, and pfmdr1 copy number and chloroquine IC50s were determined. These data were compared with LynxTag-CQGREEN uptake/fluorescence by multiple linear regression to identify genetic correlates of uptake. Uptake of the compound correlated with the logIC50 of chloroquine and, more weakly, a mutation in Pgh1, F1226Y

A haemagglutination test for rapid detection of antibodies to SARS-CoV-2

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests do not require special equipment, are read by eye, have short development times, low cost and can be applied at the Point of Care. Here we describe a quantitative Haemagglutination test (HAT) for the detection of antibodies to the receptor binding domain of the SARS-CoV-2 spike protein. The HAT has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. We will supply aliquots of the test reagent sufficient for ten thousand test wells free of charge to qualified research groups anywhere in the world