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Background: Fluoropyrimidine drugs are widely used in chemotherapy to treat solid tumors. However, severe toxicity has been reported in 10% to 40% of patients. The DPYD gene encodes the rate-limiting enzyme dihydropyrimidine dehydrogenase responsible for fluoropyrimidine catabolism. The DPYD variants resulting in decreased or no enzyme activity are associated with increased risk of fluoropyrimidine toxicity. This study aims to develop a pharmacogenetic test for screening DPYD variants to guide fluoropyrimidine therapy. Methods: A multiplex allele-specific polymerase chain reaction (AS-PCR) assay, followed by capillary electrophoresis, was developed to detect 5 common DPYD variants (c.557A > G, c.1129–5923C > G, c.1679T > G, c.1905 + 1G > A, and c.2846A > T). Deidentified population samples were used for screening positive controls and optimizing assay conditions. Proficiency testing samples with known genotypes were analyzed for test validation. All variants detected were confirmed by Sanger sequencing. Results: From the deidentified population samples, 5 samples were heterozygous for c.557A > G, 2 samples were heterozygous for c.1129–5923C > G (HapB3), and 1 sample was heterozygous for c.2846A > T. The 20 proficiency samples matched with their assigned genotypes, including 13 wild-type samples, 3 samples heterozygous for c.1679T > G, 2 samples heterozygous for c.1905 + 1G > A, and 2 samples heterozygous for c.2846A > T. One of the 3 patient samples was heterozygous for c.1129–5923C > G (HapB3). All the variants detected by the multiplex AS-PCR assay were concordant with Sanger sequencing results. Conclusions: A robust multiplex AS-PCR assay was developed to rapidly detect 5 variants in the DPYD gene. It can be used for screening DPYD variants to identify patients with increased risk of toxicity when prescribed fluoropyrimidine therapy. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study conducted in Singapore that examined the use of oral antivirals (OAVs) among older adults with COVID-19 in primary care during the Omicron waves. The study revealed that a small percentage of older adults received OAVs, with nirmatrelvir-ritonavir being the most commonly prescribed medication. The study also identified factors such as primary care characteristics and socioeconomic status (SES) indicators that influenced the likelihood of receiving OAVs. The authors emphasize the importance of addressing disparities in OAV access among older adults and socioeconomically disadvantaged groups. They recommend targeted efforts to improve access for individuals with lower SES. [Extracted from the article]

Background: The nature of speech disorders in individuals with Down Syndrome (DS) remains controversial despite various explanations put forth in the literature to account for the observed speech profiles. A high level of word production inconsistency in children with DS has led researchers to query whether the inconsistency continues into adolescence, and if the inconsistency stems from inconsistent phonological disorder (IPD) or childhood apraxia of speech (CAS). Of the studies that have been published, most suggest that the speech profile of individuals with DS is delayed, while a few recent studies suggest a combination of delayed and disordered patterns. However, no studies have explored the nature of word production inconsistency in this population, and the relationship between word production inconsistency, receptive vocabulary and severity of speech disorder. Aims: To investigate in a pilot study the extent of word production inconsistency in adolescents with DS and to examine the correlations between word production inconsistency, measures of receptive vocabulary, severity of speech disorder and oromotor skills in adolescents with DS. Methods & Procedures: The participants were 32 native speakers of Singaporean-English adolescents, comprising 16 participants with DS and 16 typically developing (TD) participants. The participants completed a battery of standardized speech and language assessments, including The Diagnostic Evaluation of Articulation and Phonology (DEAP) assessment. Results from each test were correlated to determine relationships. Qualitative analyses were also carried out on all the data collected. Outcomes & Results: In this study, seven out of 16 participants with DS scored above 40% on word production inconsistency, a diagnostic criterion for IPD. In addition, all participants with DS performed poorly on the oromotor assessment of DEAP. The overall speech profile observed did not exactly correspond with the cluster symptoms observed in children with IPD or CAS. Conclusions & Implications: Word production inconsistency is a noticeable feature in the speech of individuals with DS. In addition, the speech profiles of individuals with DS consist of atypical and unusual errors alongside developmental errors. Significant correlations were found between the measures investigated, suggesting that speech disorder in DS is multifactorial. The results from this study will help to improve differential diagnosis of speech disorders and individualized treatment plans in the population with DS.

This study followed 88 children in Beijing and Hong Kong for three years to investigate the relationships between the early teaching of literacy skills and later literacy outcomes. The children were administered the Preschool and Primary Chinese Literacy Scale at the age of five years, and three years later. Their parents and teachers reported on their involvement in literacy teaching, the home/classroom literacy environment and their beliefs about language learning. Findings showed that the Hong Kong cohort significantly surpassed their Beijing counterparts in literacy attainments at age five and age eight. After controlling for age, site, maternal education and teacher qualification, formal literacy activities in early childhood significantly contributed to literacy attainment at primary school, whereas informal literacy experiences did not. Results suggest that the complicated nature of Chinese orthography may make early instruction particularly valuable in Chinese literacy acquisition. The psycholinguistic, pedagogical and sociocontextual accounts and implications of these findings are discussed. (Contains 4 tables and 1 figure.)

The unique dimensions of perceptions of school and family contributing to depression and suicide ideation in Hong Kong adolescents were examined in two studies. In Study 1, among 327 Hong Kong Chinese female students ages 13-18, 47% reported some suicide ideation. Suicide ideation was significantly associated with depression, test anxiety, academic self-concept, and adolescents' perceived parental dissatisfaction with academic performance. The correlation between test anxiety and depression was especially high (r = 0.51). Study 2 examined how three different aspects of perceived family relationship were associated with depression and suicide ideation. Among 371 Hong Kong Chinese adolescents ages 14-20, 52.6% reported suicide ideation. Low levels of family cohesion and support and high levels of parent-adolescent conflict were positively related to depression and suicide ideation in both genders. Across both studies, depression mediated associations between academic- and family-related variables and suicide ideation. Findings underscore the importance of both academic and family climate in understanding depression and suicide ideation among Chinese adolescents.

The unique dimensions of perceptions of school and family contributing to depression and suicide ideation in Hong Kong adolescents were examined in two studies. In Study 1, among 327 Hong Kong Chinese female students ages 13-18, 47% reported some suicide ideation. Suicide ideation was significantly associated with depression, test anxiety, academic self-concept, and adolescents' perceived parental dissatisfaction with academic performance. The correlation between test anxiety and depression was especially high (r = .51). Study 2 examined how three different aspects of perceived family relationship were associated with depression and suicide ideation. Among 371 Hong Kong Chinese adolescents ages 14-20, 52.6% reported suicide ideation. Low levels of family cohesion and support and high levels of parent-adolescent conflict were positively related to depression and suicide ideation in both genders. Across both studies, depression mediated associations between academic- and family-related variables and suicide ideation. Findings underscore the importance of both academic and family climate in understanding depression and suicide ideation among Chinese adolescents.

INTRODUCTION Polymer foams having closed cells of size 10 [µmeter] or smaller and a cell density of about [10.sup.8] cells [cm.sup.-3] or higher are called microcellular foams. Such morphologies can [...]

Free radical melt grafting of glycidyl methacrylate (GMA) onto polypropylene (PP) was studied. The extent of GMA grafting and the molecular weight of the functionalized PP copolymers were controlled by carefully manipulating various reaction factors, such as monomer concentration, initiator concentration, reaction temperature, and molecular weight of the starting PP homopolymer. The use of a second monomer, styrene, in the grafting process helped to increase GMA grafting further and reduce chain scission. The GMA modified PP copolymer was found to be able to reactively compatibilize PP/acrylonitrile-co-butadiene-co-acrylic acid rubber (NBR) blends. Up to an eight-fold increase in the impact energy of the PP/NBR blend was obtained. The compatibilizing capacities of the reactive copolymers, in terms of impact energy improvement of the PP/NBR blend, were found not to be exclusively dependent on the total concentration of reactive functionalities in the matrix of the blend. The characteristics of the reactive copolymers, i.e., the extent of functionalization and the molecular weight, were found to have significant influences on the compatibilizing capacity. A large amount of moderately functionalized copolymer offers better compatibilization performance than a small amount of highly functionalized copolymer. A significant drop in impact energy was observed with declining molecular weight of the copolymer., INTRODUCTION Polymer blends have become a versatile and economically viable solution to the needs of industry for improving the performance of commodity and engineering plastics (1). However, many polymers are [...]

Background: Observational studies have shown that vitamin D binding protein (DBP) levels, a key determinant of 25-hydroxy-vitamin D (25OHD) levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease. Methods and Findings: We measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos). Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism) and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke) and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age- and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n = 2,254). DBP had a strong observational and causal association with 25OHD levels (p = 3.2 x [10.sup.-19]). While DBP levels were observationally associated with calcium and body mass index (BMI), these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI -0.01, 0.01]; p =1.00; n = 46,186); fasting insulin (0.01 pmol/l [95% CI -0.00, 0.01,]; p = 0.22; n = 46,186); BMI (0.00 kg/[m.sup.2] [95% CI -0.01, 0.01]; p = 0.80; n =127,587); bone mineral density (0.01 g/c[m.sup.2] [95% CI -0.01, 0.03]; p = 0.36; n = 32,961); mean arterial pressure (-0.06 mm Hg [95% CI -0.19, 0.07]); p = 0.36; n = 28,775); ischemic stroke (odds ratio [OR] = 1.00 [95% CI 0.97,1.04]; p = 0.92; n = 12,389/62,004 cases/controls); coronary artery disease (OR = 1.02 [95% CI 0.99, 1.05]; p = 0.31; n = 22,233/64,762); or type 2 diabetes (OR= 1.01 [95% CI 0.97, 1.05]; p = 0.76; n = 9,580/53,810). Conclusions: DBP has no demonstrable causal effect on any of the diseases or traits investigated here, except 25OHD levels. It remains to be determined whether 25OHD has a causal effect on these outcomes independent of DBP., Introduction Serum vitamin D levels are generally low in populations worldwide [1,2]. Observational studies have implicated vitamin -D-deficient states in several common diseases and related traits, including cardiovascular disease [3-5], [...]

Abstract Background Variance of peak bone mass has a substantial genetic component, as has been shown with twin studies examining quantitative measures such as bone mineral density (BMD) and quantitative ultrasound (QUS). Evidence implicating single nucleotide polymorphisms (SNPs) of the transforming growth factor beta-1 (TGFB1) gene is steadily accumulating. However, a comprehensive look at multiple SNPs at this locus for their association with indices of peak bone mass has not been reported. Methods A cohort of 653 healthy Caucasian females 18 to 35 years old was genotyped for seven TGFB1 SNPs. Polymorphisms were detected by restriction endonuclease digestion of amplified DNA segments. Results The frequencies of the least common allele at G-800A, C-509T, codon 10 (L10P), codon 25 (R25P), codon 263 (T263I), C861-20T, and 713-8 delC loci were 0.07, 0.33, 0.41, 0.08, 0.04, 0.25 and 0.01, respectively. A significant association was seen between QUS Stiffness Index (QUS-SI) and the SNP at codon 10 and the linked promoter SNP, C-509T. This association remained significant after multiple regression was used to incorporate important clinical covariates – age, BMI, level of activity, family history, and caffeine intake – into the model. Conclusion The association of QUS-SI with -509T is consistent with a gene-dose effect, while only individuals homozygous for the codon 10P allele showed a significant increase. In this cohort of young healthy Caucasian females, the T allele at position -509 is associated with greater bone mass as measured by calcaneal ultrasound.