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1.
Nutrients ; 16(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38732602

ABSTRACT

Early childhood caries (ECC) is a growing public health concern worldwide. Although numerous systematic reviews have been published regarding the association between breastfeeding and early childhood caries (ECC), the results remain inconclusive and equivocal. This systematic review synthesises the evidence on the association between breastfeeding and ECC. Five electronic databases and backward citation chasing were performed from inception until May 2023. A total of 31 studies (22 cohort studies and 9 case-control studies) were included in this review. The meta-analysis of the case-control studies showed statistically significant fewer dental caries in children who were breastfed for < 6 months compared to those who were breastfed for ≥6 months (OR = 0.53, 95% CI 0.41-0.67, p < 0.001). There was a statistically significant difference in dental caries between children who were breastfed for <12 months and those who were breastfed for ≥12 months (RR = 0.65, 95% CI 0.50-0.86, p < 0.002). Similarly, there was a statistically significant difference in dental caries in children who were breastfed for < 18 months compared to those who were breastfed for ≥18 months (RR = 0.41, 95% CI 0.18-0.92, p = 0.030). Nocturnal breastfeeding increases the risk of ECC compared with no nocturnal breastfeeding (RR = 2.35, 95% CI 1.42-3.89, p < 0.001). The findings suggest breastfeeding for more than 12 months and nocturnal breastfeeding increase the risk of ECC.


Subject(s)
Breast Feeding , Dental Caries , Breast Feeding/statistics & numerical data , Humans , Dental Caries/epidemiology , Dental Caries/etiology , Child, Preschool , Infant , Female , Risk Factors , Male , Case-Control Studies
2.
Front Robot AI ; 11: 1328467, 2024.
Article in English | MEDLINE | ID: mdl-38721395

ABSTRACT

Social-educational robotics, such as NAO humanoid robots with social, anthropomorphic, humanlike features, are tools for learning, education, and addressing developmental disorders (e.g., autism spectrum disorder or ASD) through social and collaborative robotic interactions and interventions. There are significant gaps at the intersection of social robotics and autism research dealing with how robotic technology helps ASD individuals with their social, emotional, and communication needs, and supports teachers who engage with ASD students. This research aims to (a) obtain new scientific knowledge on social-educational robotics by exploring the usage of social robots (especially humanoids) and robotic interventions with ASD students at high schools through an ASD student-teacher co-working with social robot-social robotic interactions triad framework; (b) utilize Business Model Canvas (BMC) methodology for robot design and curriculum development targeted at ASD students; and (c) connect interdisciplinary areas of consumer behavior research, social robotics, and human-robot interaction using customer discovery interviews for bridging the gap between academic research on social robotics on the one hand, and industry development and customers on the other. The customer discovery process in this research results in eight core research propositions delineating the contexts that enable a higher quality learning environment corresponding with ASD students' learning requirements through the use of social robots and preparing them for future learning and workforce environments.

3.
Children (Basel) ; 11(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38671632

ABSTRACT

In Australia, dental caries are observed in almost half of children starting school. Oral health promotion programs are being implemented in early childhood education and care (ECEC) settings to promote oral health. This study examined children's perceptions of one such program, the Bright Smiles Bright Futures (BSBF) program in ECEC settings in New South Wales, Australia. Data were collected using focus group discussions from 15 children aged 3-5 years, transcribed verbatim, and analysed through inductive thematic analysis. Three themes were identified as follows: (i) oral health knowledge of children, (ii) oral hygiene practices routine and skills development, and (iii) evaluation of the oral health promotion kit and opportunities for improvement. Children's perspectives highlight the BSBF program's success in communicating key messages to promote oral health. The integration of family-centric approaches, acknowledgement of children's preferences, and the use of interactive tools collectively enhance the overall effectiveness of the oral health promotion program.

4.
Mycopathologia ; 189(2): 23, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38407762

ABSTRACT

Innate and adaptive immunity play a crucial role in allergic bronchopulmonary aspergillosis (ABPA) pathogenesis. We performed next-generation sequencing using the Illumina TruSight One panel (4,811 human disease-associated genes, at least 20 × coverage) and selected 22 known immune genes (toll-like receptors (TLRs), C-type lectin, interleukin-4 receptor, and others). We included ABPA (n = 18), asthma without ABPA (n = 12), and healthy controls (n = 8). We analyzed 3011 SNPs from 22 genes and identified 145 SNPs (13 genes) that were present only in the disease groups and absent in controls. The SNP frequency overall was significantly higher in ABPA than in asthmatics (89/145 [61.4%] vs. 56/145 [38.6%], p = 0.0001). The SNP frequency in the TLR10 gene was also significantly higher in ABPA than in asthma (p = 0.017). Association analysis further revealed three genes having significant associations. Of these, NOS3 and HLA-DQB1 are associated with antimicrobial activity and adaptive immunity. More extensive studies are required to confirm our findings.


Subject(s)
Aspergillosis, Allergic Bronchopulmonary , Asthma , Humans , Aspergillosis, Allergic Bronchopulmonary/complications , Aspergillosis, Allergic Bronchopulmonary/genetics , Polymorphism, Single Nucleotide , Asthma/complications , Asthma/genetics , High-Throughput Nucleotide Sequencing , Lectins, C-Type
5.
Indian J Med Microbiol ; 48: 100537, 2024.
Article in English | MEDLINE | ID: mdl-38350525

ABSTRACT

PURPOSE: Tuberculosis is an important public health problem among infectious diseases. The problem becomes more concerning with the emergence of MDR-TB and pre-XDR-TB. Whole genome sequencing (WGS) detection of resistance has recently gained popularity as it has advantages over other commercial techniques. METHODS: We performed in-house WGS followed by detailed analysis by an in-house pipeline to identify the resistance markers. This was accompanied by Phenotypic DST, and Sanger sequencing on all the 12 XDR, 06 pre-XDR, and 06 susceptible M. tb isolates. These results were collated with online M. tb WGS pipelines (TB profiler, PhyResSE, Mykrobe predictor) for comparative analysis. RESULTS: Following our in-house analysis, we observed 64 non-synonymous SNPs, fifteen synonymous SNPs, and five INDELs in 25 drug resistance-associated genes/intergenic regions (IGRs) in M. tb isolates. Sensitivity for detecting XDR is 33%, 58%, 83%, and 83%, respectively, using Mykrobe predictor, PhyResSE, TB-profiler, and in-house pipeline for WGS analysis, respectively. TB-profiler detected a rare mutation H70R in the gyrA gene in one pre-XDR isolate. Lineage 2.2.1 East-Asian (Beijing sublineage type) predominated (60%) in WGS data analysis of the XDR isolates. CONCLUSIONS: Our findings suggest that in-house analysis of WGS data and TB-profiler sensitivity was better for the detection of second-line resistance as compared to other automated tested tools. Frequent upgradation of newer mutations associated with resistance needs to be updated, as it potentiates tailored treatment for patients.


Subject(s)
Mycobacterium tuberculosis , Polymorphism, Single Nucleotide , Whole Genome Sequencing , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/classification , India , Humans , Tuberculosis, Multidrug-Resistant/microbiology , Microbial Sensitivity Tests , Antitubercular Agents/pharmacology , Genome, Bacterial/genetics , Extensively Drug-Resistant Tuberculosis/microbiology
6.
ACS Infect Dis ; 10(1): 138-154, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38146853

ABSTRACT

Biofilm infections are mainly caused by Gram-positive bacteria (GPB) like Staphylococcus aureus, Gram-negative bacteria (GNB) like Pseudomonas aeruginosa, and fungi like Candida albicans. These infections are responsible for antimicrobial tolerance, and commensal interactions of these microbes pose a severe threat to chronic infections. Treatment therapies against biofilm infections are limited to eradicating only 20-30% of infections. Here, we present the synthesis of a series of bile acid-derived molecules using lithocholic acid, deoxycholic acid, and cholic acid where two bile acid molecules are tethered through 3'-hydroxyl or 24'-carboxyl terminals with varying spacer length (trimethylene, pentamethylene, octamethylene, and dodecamethylene). Our structure-activity relationship investigations revealed that G21, a cholic acid-derived gemini amphiphile having trimethylene spacer tethered through the C24 position, is a broad-spectrum antimicrobial agent. Biochemical studies witnessed that G21 interacts with negatively charged lipoteichoic acid, lipopolysaccharide, and phosphatidylcholine moieties of GPB, GNB, and fungi and disrupts the microbial cell membranes. We further demonstrated that G21 can eradicate polymicrobial biofilms and wound infections and prevent bacteria and fungi from developing drug resistance. Therefore, our findings revealed the potential of G21 as a versatile antimicrobial agent capable of effectively targeting polymicrobial biofilms and wound infections, suggesting that it is a promising antimicrobial agent for future applications.


Subject(s)
Anti-Infective Agents , Cyclopropanes , Wound Infection , Humans , Cholic Acid/pharmacology , Anti-Infective Agents/pharmacology , Bile Acids and Salts/pharmacology , Biofilms , Wound Infection/drug therapy , Gram-Positive Bacteria
7.
Article in English | MEDLINE | ID: mdl-38015333

ABSTRACT

Gallstone disease (GSD) is a prevalent health condition that impacts many adults and is associated with presence of stones in gallbladder cavity that results in inflammation, pain, fever, nausea and vomiting. Several genome-wide association studies (GWAS) in the past have identified genes associated with GSD but only a few were focused on Latino population. To identify genetic risk factors for GSD in Latino population living in the Southwest USA we used self-reported clinical history, physical and lab measurements data in Sangre Por Salud (SPS) cohort and identified participants with and without diagnosis of GSD. We performed a GWAS on this phenotype using GSD cases matched to normal controls based on a tight criterion. We identified several novel loci associated with GSD as well as loci that were previously identified in past GWAS studies. The top 3 loci (MATN2, GPRIN3, GPC6) were strongly associated with GSD phenotype in our combined analysis and a sex stratified analysis results in females were closest to the overall results reflecting a general higher disease prevalence in females. The top identified variants in MATN2, GPRIN3, and GPC6 remain unchanged after local ancestry adjustment in SPS Latino population. Follow-up pathway enrichment analysis suggests enrichment of GO terms that are associated with immunological pathways; enzymatic processes in gallbladder, liver, and gastrointestinal tract; and GSD pathology. Our findings suggest an initial starting point towards better and deeper understanding of differences in gallstone disease pathology, biological mechanisms, and disease progression among Southwest US Latino population.

8.
medRxiv ; 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37986981

ABSTRACT

Introduction: The goal of this study was to evaluate the association between a polygenic risk score (PRS) for QT prolongation (QTc-PRS), QTc intervals and mortality in patients enrolled in the UK Biobank with and without sleep apnea. Methods: The QTc-PRS was calculated using allele copy number and previously reported effect estimates for each single nuclear polymorphism SNP. Competing-risk regression models adjusting for age, sex, BMI, QT prolonging medication, race, and comorbid cardiovascular conditions were used for sudden cardiac death (SCD) analyses. Results: 500,584 participants were evaluated (56.5 ±8 years, 54% women, 1.4% diagnosed with sleep apnea). A higher QTc-PRS was independently associated with the increased QTc interval duration (p<0.0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile (p<0.001). Sleep apnea was found to be an effect modifier in the relationship between QTc-PRS and SCD. The adjusted HR per 5-unit change in QTc-PRS for SCD was 1.64 (95% CI 1.16 - 2.31, p=0.005) among those with sleep apnea and 1.04 (95% CI 0.95 - 1.14, p=0.44) among those without sleep apnea (p for interaction =0.01). Black participants with sleep apnea had significantly elevated adjusted risk of SCD compared to White participants (HR=9.6, 95% CI 1.24 - 74, p=0.03). Conclusion: In the UK Biobank population, the QTc-PRS was associated with SCD among participants with sleep apnea but not among those without sleep apnea, indicating that sleep apnea is a significant modifier of the genetic risk. Black participants with sleep apnea had a particularly high risk of SCD.

9.
BMC Oral Health ; 23(1): 769, 2023 10 19.
Article in English | MEDLINE | ID: mdl-37858057

ABSTRACT

BACKGROUND: People with Intellectual and developmental disabilities (IDDs) experience oral health inequality due to myriad of risk factors and complex needs. Sensory processing difficulties, maladaptive behaviours and dental anxiety contribute to difficulties in receiving preventive and routine dental treatments. This study aimed to systematically review the evidence on the effectiveness of sensory adaptive dental environments (SADE) for children and young adults (up to the ages 24 years) with IDD to address cooperation and dental anxiety. METHODS: This review was reported according to The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. MEDLINE (Ovid), The Cochrane Library, Embase, Google Scholar, Web of Science and OT Seeker were searched using appropriate terms to identify Randomised Control Trails (RCTs) that matched inclusion criteria. Screening was conducted by two reviewers after de-duplication based on titles and abstracts followed by full text retrieval. Quality of the included studies was assessed using Cochrane Risk of Bias (ROB)-2 for crossover trials and data extracted by two reviewers. The details of the interventions and effectiveness were compared and discussed narratively, and comparable outcomes were included to meta-analyses using R software. RESULTS: A total of 622 articles were identified and five articles met eligibility for inclusion. Three studies used multi-sensory adaptations and one used single sensory adaptation of music. Narrative synthesis showed some evidence of SADE reducing magnitude and duration, although, questionable for reducing the number of maladaptive behaviours. Two studies demonstrated conflicting evidence of the effect of SADE on cooperation. Three studies demonstrated significant positive impact of SADE on psychophysiological outcomes. Despite an overall tendency to favour SADE, no statistically significant difference of maladaptive behaviours was found between SADE and regular dental environment (RDE) (Standardised mean change (SMC) = 0.51; 95% Confidence Interval (CI) -0.20 to 1.22; p = 0.161). SADE was superior to RDE (SMC -0.66; 95% CI -1.01 to -0.30; p = < 0.001) in reducing psychophysiological responses of dental anxiety. CONCLUSION: Current evidence suggests that adapting visual, tactile, and auditory aspects of the dental environment in a single or multi-sensory approach demonstrates small positive effects on psychophysiological responses and maladaptive behaviours of dental anxiety for people with IDD. TRIAL REGISTRATION: The title of this review was registered with PROSPERO (CRD42022322083).


Subject(s)
Dental Anxiety , Developmental Disabilities , Child , Humans , Young Adult , Dental Anxiety/prevention & control , Oral Health , Psychophysiology , Risk Factors
10.
Public Health Nutr ; 26(12): 3147-3161, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37905557

ABSTRACT

OBJECTIVE: To conduct a systematic review of experimental or quasi-experimental studies that aimed to improve the nutritional status of children under 5 years of age in Ethiopia. DESIGN: Embase, MEDLINE/PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsychINFO, and Academic Search Database were used to locate peer-reviewed studies, and Google Scholar and Open Dissertation were used to locate grey literatures. All searches were conducted between 2000 and November 2022. SETTING: Ethiopia. PARTICIPANTS: Pregnant women and mothers with children aged 0-59 months. RESULTS: Ten cluster randomised controlled trials (RCT), six quasi-experimental studies and two individual RCT were included. Out of the identified eighteen studies, three studies targeted pregnant mothers. Our findings showed that almost two-thirds of published interventions had no impact on childhood stunting and wasting, and more than half had no impact on underweight. Some behaviour change communication (BCC) interventions, food vouchers, micronutrient supplementation and quality protein maize improved stunting. Similarly, BCC and fish oil supplementation showed promise in reducing wasting, while BCC and the provision of quality protein maize reduced underweight. Additionally, water, sanitation and hygiene (WaSH) interventions provided to pregnant mothers and children under 2 years of age were shown to significantly reduce childhood stunting. CONCLUSION: Future childhood nutritional interventions in Ethiopia should consider adopting an integrated approach that combines the positive effects of interdependent systems such as BCC, food supplemental programmes (e.g. boosting protein and micronutrients), health interventions (e.g. strengthening maternal and childcare), WaSH and financial initiatives (e.g. monetary support and income schemes).


Subject(s)
Nutritional Status , Thinness , Child , Female , Pregnancy , Humans , Infant , Child, Preschool , Ethiopia , Dietary Supplements , Growth Disorders
12.
Exp Parasitol ; 255: 108630, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37820893

ABSTRACT

INTRODUCTION: The free-living protozoan Acanthamoeba can cause severe keratitis known as Acanthamoeba Keratitis (AK) and granulomatous amoebic encephalitis (GAE). The pathogenesis of Acanthamoeba includes intricate interactions between the organism and the host's immune system. The downstream analysis of a well-annotated genome assembly along with proteomic analysis can unravel several biological processes and aid in the identification of potential genes involved in pathogenicity. METHODS: Based on the next-generation sequencing data analysis, genes including lysophospholipase, phospholipase, S8/S53 peptidase, carboxylesterase, and mannose-binding protein were selected as probable pathogenic targets that were validated by conventional PCR in a total of 30 Acanthamoeba isolates. This was followed by real-time PCR for the evaluation of relative gene expression in the keratitis and amoebic encephalitis animal model induced using keratitis (CHA5), encephalitis (CHA24) and non-pathogenic environmental isolate (CHA36). In addition, liquid chromatography-mass spectrometry (LC-MS/MS) was performed for keratitis, encephalitis, and non-pathogenic environmental isolate before and after treatment with polyhexamethylene biguanide (PHMB). RESULTS: The conventional PCR demonstrated the successful amplification of lysophospholipase, phospholipase, S8/S53 peptidase, carboxylesterase, and mannose-binding protein genes in clinical and environmental isolates. The expression analysis revealed phospholipase, lysophospholipase, and mannose-binding genes to be significantly upregulated in the keratitis isolate (CHA 5) during AK in the animal model. In the case of the amoebic encephalitis model, phospholipase, lysophospholipase, S8/S53 peptidase, and carboxylesterase were significantly upregulated in the encephalitis isolate compared to the keratitis isolate. The proteomic data revealed differential protein expression in pathogenic versus non-pathogenic isolates in the pre and post-treatment with PHMB. CONCLUSION: The gene expression data suggests that lysophospholipase, phospholipase, S8/S53 peptidase, carboxylesterase, and mannose-binding protein (MBP) could play a role in the contact-dependent and independent mechanisms of Acanthamoeba pathogenesis. In addition, the proteomic profiling of the 3 isolates revealed differential protein expression crucial for parasite growth, survival, and virulence. Our results provide baseline data for selecting possible pathogenic targets that could be utilized for designing knockout experiments in the future.


Subject(s)
Acanthamoeba Keratitis , Acanthamoeba , Amebiasis , Encephalitis , Mannose-Binding Lectin , Animals , Lysophospholipase/genetics , Chromatography, Liquid , Proteomics , Tandem Mass Spectrometry , Acanthamoeba Keratitis/parasitology , Amebiasis/parasitology , Real-Time Polymerase Chain Reaction , Gene Expression , Peptide Hydrolases
13.
BMC Pediatr ; 23(1): 467, 2023 09 16.
Article in English | MEDLINE | ID: mdl-37716969

ABSTRACT

BACKGROUND: Regular growth monitoring can be used to evaluate young children's nutritional and physical health. While adequate evaluation of the scope and quality of nutrition interventions is necessary to increase their effectiveness, there is little research on growth monitoring coverage measurement. The purpose of this study was to investigate socioeconomic disparities in under-5 Rwandan children who participate in growth monitoring and nutrition promotion. METHODS: We used data from the 2019-2020 Rwanda Demographic and Health Survey (RDHS), which included 8092under-5 children. Percentage was employed in univariate analysis. To examine the socioeconomic inequalities, concentration indices and Lorenz curves were used in growth monitoring and nutrition promotion among under-5 children. RESULTS: A weighted prevalence of 33.0% (95%CI: 30.6-35.6%) under-5 children growth monitoring and nutrition promotion was estimated. Growth monitoring and nutrition promotion among under-5 children had higher uptake in the most disadvantaged cohort, as the line of equality sags below the diagonal line in Lorenz curve. Overall, there was pro-poor growth monitoring and nutrition promotion among under-5 in Rwanda (Conc. Index = 0.0994; SE = 0.0111). Across the levels of child and mother's characteristics, the results show higher coverage of under-5 growth monitoring and nutrition promotion in the most socioeconomic disadvantaged cohort. CONCLUSION: The study found a pro-poor disparity in growth monitoring and nutrition promotion among under-5 children in Rwanda. By implication, the most disadvantaged children had a higher uptake of growth monitoring and nutrition promotion. The Rwanda government should develop policies and programmes to achieve the universal health coverage for the well-off and underserved population.


Subject(s)
Nutritional Status , Socioeconomic Disparities in Health , Child , Humans , Child, Preschool , Rwanda , Research Design , Universal Health Insurance
14.
J Proteomics ; 287: 104974, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37467891

ABSTRACT

To identify and evaluate differentially expressed plasma proteins in biliary atresia (BA), we performed plasma proteome profiling using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 20 patients with BA and 10 control children. Serological assays validated the most significant and highly upregulated proteins in a cohort of 45 patients and 15 controls. Bioinformatics tools were used for functional classification and protein-protein interactions of differentially expressed proteins (DEPs). Of 405 proteins detected in patients and 360 in controls, 242 proteins, each with ≥2 unique peptides (total of 3230 peptides), were common in both groups. Compared to controls, 90 proteins in patients were differentially expressed and were dysregulated. Twenty-five were significantly upregulated with polymeric immunoglobulin receptor (PIgR), galectin-3-binding protein (Gal-3BP), complement C2, the most prominent, and 15 had low expression. The bioinformatic analysis revealed functional interaction between DEPs and their role in an inflammatory immune response. Enzyme immunoassay for PIgR and Gal-3BP in patients' plasma showed their levels raised significantly (p = 0.0021 and p = 0.0369, respectively). The PIgR and Gal-3BP are novel proteins upregulated in BA and may be tested further for their utility as potential circulating disease biomarker(s). SIGNIFICANCE: The study shows that plasma PIgR and GAL-3BP levels are significantly raised in infants with BA within the first 3 months of life. If tested in a larger cohort, these proteins may be found to have their diagnostic potential and utility as disease biomarkers. The study also provides valuable information on the involvement of several DEPs in innate immune response, chronic inflammation, and fibrosis. This strengthens the hypothesis that the immune-mediated inflammatory processes are responsible for the progressive nature of BA.


Subject(s)
Biliary Atresia , Receptors, Polymeric Immunoglobulin , Child , Humans , Infant , Chromatography, Liquid , Galectin 3/metabolism , Proteomics , Tandem Mass Spectrometry
15.
Age Ageing ; 52(6)2023 06 01.
Article in English | MEDLINE | ID: mdl-37261448

ABSTRACT

BACKGROUND: Older people are often explicitly or implicitly excluded from research, in particular clinical trials. This means that study findings may not be applicable to them, or that older people may not be offered treatments due to an absence of evidence. AIMS: The aim of this work was to develop recommendations to guide all research relevant to older people. METHODS: A diverse stakeholder group identified barriers and solutions to including older people in research. In parallel, a rapid literature review of published papers was undertaken to identify existing papers on the inclusion of older people in research. The findings were synthesised and mapped onto a socio-ecological model. From the synthesis we identified themes that were developed into initial recommendations that were iteratively refined with the stakeholder group. RESULTS: A range of individual, interpersonal, organisational, community and policy factors impact on the inclusion of older people in research. A total of 14 recommendations were developed such as removing upper age limits and comorbidity exclusions, involving older people, advocates and health and social care professionals with expertise in ageing in designing the research, and considering flexible or alternative approaches to data collection to maximise opportunities for participation. We also developed four questions that may guide those developing, reviewing and funding research that is inclusive of older people. CONCLUSION: Our recommendations provide up to date, practical advice on ways to improve the inclusion of older people in health and care research.


Subject(s)
Aging , Social Support , Humans , Aged
16.
Lancet Reg Health Southeast Asia ; 8: 100094, 2023 Jan.
Article in English | MEDLINE | ID: mdl-37384142

ABSTRACT

Background: Diphtheria, Tetanus, and whole-cell Pertussis (DTwP) vaccination-associated seizures form the commonest type of serious adverse event following immunization in India and are an important reason for vaccine hesitancy. Our study explored the genetic explanation of DTwP vaccination-associated seizures or subsequent epilepsies. Methods: Between March 2017 and March 2019, we screened 67 children with DTwP vaccination-associated seizures or subsequent epilepsies, and of those, we studied 54 without prior seizures or neurodevelopmental deficits. Our study design was cross-sectional with a 1-year follow-up having both retrospective and prospective cases. We performed clinical exome sequencing focused on 157 epilepsy-associated genes and multiplex ligation-dependent probe amplification of the SCN1A gene at enrolment. We applied the Vineland Social Maturity Scale for neurodevelopmental assessment at follow-up. Findings: Of 54 children enrolled and underwent genetic testing (median age 37.5 months, interquartile range 7.7-67.2; diagnosis at enrolment: epilepsy 29, febrile seizure 21, and febrile seizure-plus 4), we found 33 pathogenic variants of 12 genes. Of 33 variants, 13 (39%) were novel. Most pathogenic variants were found in SCN1A gene (n = 21/33; 64%), SCN8A in 2 children, and 10 children had one variant in CDKL5, DEPDC5, GNAO1, KCNA2, KCNT1, KCNQ2, NPRL3, PCDH19, RHOBTB2, and SLC2A1. Five or more seizures (odds ratio [OR] = 5.3, confidence interval [CI]: 1.6-18.4, p = 0.006), drug-resistant epilepsy (OR = 9.8, 95% CI: 2.6-30.7, p = 0.001) and neurodevelopmental impairment (social quotient < 70) (OR = 5.6, 95% CI: 1.65-17.6, p = 0.006) were significant predictors of genetic diagnosis. Interpretation: Our study provides proof-of-concept for genetic aetiology in children with DTwP vaccination-associated seizures or subsequent epilepsies and has important implications for vaccination policies in developing countries. Funding: International Pediatric Association Foundation, Inc. (IPAF): Ihsan Dogramaci research award 2016/2017; Indian Council of Medical Research (ICMR), New Delhi, India: No.3/1/3/JRF-2016/HRD/LS/71/10940.

17.
Cancers (Basel) ; 15(12)2023 Jun 08.
Article in English | MEDLINE | ID: mdl-37370729

ABSTRACT

Liquid biopsy is a revolutionary tool that is gaining momentum in the field of cancer research. As a body fluid, urine can be used in non-invasive diagnostics for various types of cancer. We investigated the performance of UAS™ as a preservative for urinary analytes. Firstly, the need for urine preservation was investigated using urine samples from healthy volunteers. Secondly, the performance of UAS™ was assessed for cell-free DNA (cfDNA) and host cell integrity during storage at room temperature (RT) and after freeze-thaw cycling. Finally, UAS™ was used in a clinical setting on samples from breast and prostate cancer patients. In the absence of a preservative, urinary cfDNA was degraded, and bacterial overgrowth occurred at RT. In urine samples stored in UAS™, no microbial growth was seen, and cfDNA and cellular integrity were maintained for up to 14 days at RT. After freeze-thaw cycling, the preservation of host cell integrity and cfDNA showed significant improvements when using UAS™ compared to unpreserved urine samples. Additionally, UAS™ was found to be compatible with several commercially available isolation methods.

18.
BMJ Open ; 13(5): e069756, 2023 05 10.
Article in English | MEDLINE | ID: mdl-37164458

ABSTRACT

OBJECTIVES: This study aimed to analyse the usability, content, readability and cultural appropriateness of alcohol and other drugs (AODs) resources for Aboriginal and Torres Strait Islander Peoples in New South Wales (NSW), Australia. OUTCOME MEASURES: The content of 30 AOD resources for Aboriginal and Torres Strait Islander Peoples was analysed according to the following criteria: general characteristics; elements of graphical design and written communication; thoroughness and content; readability (Flesch-Kincaid grade level (FKGL), Gunning Fog index (Fog), Simplified Measure of Gobbledygook and Flesch Reading Ease); and cultural appropriateness. RESULTS: Most resources displayed good usability, depicted by the use of headings and subheadings (n=27), superior writing style (n=19), relevant visuals (n=19) and use of colour support (n=30). However, some resources used at least one professional jargon (n=13), and many did not provide any peer-reviewed references (n=22). During content analysis, 12 resources were categorised into the alcohol group and 18 resources in the other drugs group. Impact of alcohol during pregnancy and breast feeding (n=12) was the most common included topics in the resources related to alcohol, while the physical impact of drugs (n=15) was the most discussed topics among the other drugs group. Based on the FKGL readability score, 83% of resources met the recommended reading grade level of 6-8 by NSW Health. Many resources (n=21) met at least half of the cultural appropriateness elements of interest. However, less than one-third were developed in collaboration with the local community (n=9), used local terms (n=5), targeted the local community (n=3), included an Aboriginal voice (n=2) and addressed the underlying cause (n=1). CONCLUSIONS: Many AOD resources are developed specifically for Aboriginal and Torres Strait Islander Peoples, but their usability, content and readability differed, and they were not culturally appropriate for all communities. Development of a standardised protocol for resource development is suggested.


Subject(s)
Australian Aboriginal and Torres Strait Islander Peoples , Health Services, Indigenous , Humans , New South Wales , Comprehension , Australia
19.
Open Forum Infect Dis ; 10(4): ofad111, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37065988

ABSTRACT

Background: Data on respiratory syncytial virus (RSV) disease burden in adults remain scarce. We assessed the burden of confirmed RSV-acute respiratory infections (cRSV-ARIs) in community-dwelling (CD) adults and those in long-term care facilities (LTCFs). Methods: In this prospective cohort study covering 2 RSV seasons (October 2019-March 2020 and October 2020-June 2021), RSV-ARIs were identified through active surveillance, in medically stable CD-adults ≥50 years (Europe) or adults ≥65 years in LTCFs (Europe and the United States). RSV infection was confirmed by polymerase chain reaction from combined nasal and throat swabs. Results: Of 1981 adults enrolled, 1251 adults in CD and 664 LTCFs (season 1) and 1223 adults in CD and 494 LTCFs (season 2) were included in the analyses. During season 1, overall incidence rates ([IRs] cases/1000 person-years) and attack rates (ARs) for cRSV-ARIs were 37.25 (95% confidence interval [CI], 22.62-61.35) and 1.84% in adults in CD and 47.85 (CI, 22.58-101.4) and 2.26% in adults in LTCFs. Complications occurred for 17.4% (CD) and 13.3% (LTCFs) of cRSV-ARIs. One cRSV-ARI occurred in season 2 (IR = 2.91 [CI, 0.40-20.97]; AR = 0.20%), without complications. No cRSV-ARIs led to hospitalization or death. Viral pathogens were codetected in ≤17.4% of cRSV-ARIs. Conclusions: RSV is an important cause of disease burden in adults in CD and LTCFs. Despite the observed low severity of cRSV-ARI, our results support the need for RSV prevention strategies among adults ≥50 years old.

20.
Cancer Med ; 12(11): 12792-12801, 2023 06.
Article in English | MEDLINE | ID: mdl-37081700

ABSTRACT

BACKGROUND: The United States is becoming increasingly diverse, but few molecular studies have assessed the progression of clear cell renal cell carcinoma (ccRCC) in diverse patient populations. This study examined ccRCC molecular variations in non-Hispanic White (NHW) and Hispanic patients and their effect on the association of gene expression with high-grade (Grade 3 or 4) ccRCC and overall mortality. METHODS: A total of 156 patients were included in VHL sequencing and/or TempO-Seq analysis. DESeq2 was used to identify the genes associated with high-grade ccRCC. Logistic regression analysis was performed to assess whether race and ethnicity was associated with high/moderate impact VHL somatic mutations and the ccA/ccB subtype. Cox regression analysis was performed to assess association of molecular subtype and gene expression with overall mortality. RESULTS: NHWs had moderate or high impact mutations in the VHL gene at a higher frequency than Hispanics (40.2% vs. 27.4%), while Hispanics had a higher frequency of the ccA subtype than NHWs (61.9% vs. 45.8%). ccA was more common in patients with BMI≥35 (65.2%) than in those with BMI < 25 (45.0%). There were 11 differentially expressed genes between high- and low-grade tumors. The Haptoglobin (HP) gene was most significantly overexpressed in high- compared to low-grade ccRCC in all samples (p-adj = 1.7 × 10-12 ). When stratified by subtype, the 11 genes were significantly differentially expressed in the ccB subtype, but none of them were significant after adjusting for multiple testing in ccA. Finally, patients with the ccB subtype had a significantly increased risk of overall mortality (HR 4.87; p = 0.01) compared to patients with ccA, and patients with high HP expression and ccB, had a significantly increased risk of mortality compared to those with low HP expression and ccA (HR 6.45, p = 0.04). CONCLUSION: This study reports ccRCC molecular variations in Hispanic patients who were previously underrepresented.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , White , Hispanic or Latino/genetics , Ethnicity
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