Machine learning reveals the rules governing the efficacy of mesenchymal stromal cells in septic preclinical models.

BACKGROUND: Mesenchymal Stromal Cells (MSCs) are the preferred candidates for therapeutics as they possess multi-directional differentiation potential, exhibit potent immunomodulatory activity, are anti-inflammatory, and can function like antimicrobials. These capabilities have therefore encouraged scientists to undertake numerous preclinical as well as a few clinical trials to access the translational potential of MSCs in disease therapeutics. In spite of these efforts, the efficacy of MSCs has not been consistent-as is reflected in the large variation in the values of outcome measures like survival rates. Survival rate is a resultant of complex cascading interactions that not only depends upon upstream experimental factors like dosage, time of infusion, type of transplant, etc.; but is also dictated, post-infusion, by intrinsic host specific attributes like inflammatory microniche including proinflammatory cytokines and alarmins released by the damaged host cells. These complex interdependencies make a researcher's task of designing MSC transfusion experiments challenging. METHODS: In order to identify the rules and associated attributes that influence the final outcome (survival rates) of MSC transfusion experiments, we decided to apply machine learning techniques on manually curated data collected from available literature. As sepsis is a multi-faceted condition that involves highly dysregulated immune response, inflammatory environment and microbial invasion, sepsis can be an efficient model to verify the therapeutic effects of MSCs. We therefore decided to implement rule-based classification models on data obtained from studies involving interventions of MSCs in sepsis preclinical models. RESULTS: The rules from the generated graph models indicated that survival rates, post-MSC-infusion, are influenced by factors like source, dosage, time of infusion, pre-Interleukin-6 (IL-6)/ Tumour Necrosis Factor- alpha (TNF-α levels, etc. CONCLUSION: This approach provides important information for optimization of MSCs based treatment strategies that may help the researchers design their experiments.

Urban-rural disparities and change in postnatal care use from 2016 to 2019 in Ethiopia: Multivariate decomposition analysis.

BACKGROUND: Postnatal care (PNC) is essential for early identification and management of life-threatening obstetric complications. Despite efforts by the Ethiopian government to improve maternal and child health service use, PNC service has remained low, and disparity across geographic locations is a major public health problem. This study aimed to investigate the change and contributing factors in PNC service use across geographical locations (rural-urban) and over time (2016 to 2019) in Ethiopia. METHODS: We analyzed data on women who gave birth from the 2016 and 2019 Ethiopian Demographic and Health Surveys. A total of 6,413 weighted samples (4,308 in 2016 and 2,105 in 2019) were included in the analysis. A multivariate decomposition analysis technique was used to determine the change and identify factors that contributed to the change across geographical locations and over time. Statistical significance was defined at a 95% confidence interval with a p-value of less than 0.05. RESULTS: The prevalence of PNC use was higher among urban residents, and the urban-rural disparity reduced from 32.59% in 2016 to 19.08% in 2019. The difference in the composition of explanatory variables was the only statistically significant for the urban-rural disparity in PNC use in both surveys. Specifically, female household heads (4.51%), delivery at a health facility (83.45%), and birth order of two to three (5.53%) and four or more (-12.24%) in 2016 significantly contributed to the urban-rural gap. However, in 2019, middle wealth index (-14.66%), Muslim religion (3.84%), four or more antennal care contacts (18.29%), and delivery at a health facility (80.66%) significantly contributed to the urban-rural gap. PNC use increased from 16.61% in 2016 to 33.86% in 2019. About 60% of the explained change was due to the difference in the composition of explanatory variables. Particularly, urban residence (-5.79%), a rich wealth index (2.31%), Muslim (3.42%), and other (-2.76%) religions, having radio or television (1.49%), 1-3 (-1.13%), and 4 or more (11.09%) antenatal care contacts, and delivery at a health facility (47.98%) were statistically significant contributors to the observed change. The remaining 40% of the overall change was due to the difference in unknown behaviors (coefficient) of the population towards PNC. CONCLUSIONS: There was a significant change in PNC service use by residence location and over time in Ethiopia, with urban women in both surveys being more likely to use PNC service. The urban-rural disparity in PNC uptake was due to the difference in the composition of explanatory variables, whereas the change over time was due to the change in both the composition of explanatory variables and population behavior towards PNC. Increased antenatal care contacts and delivery at a health facility played a major role in explaining the gap in PNC services across residences and over time in Ethiopia, highlighting the importance of stepping up efforts to enhance their uptake in rural settings.

Community-based health insurance beneficiaries' satisfaction on laboratory services and associated factors in selected public hospitals in Jimma Zone, Oromia Region, Southwest, Ethiopia.

BACKGROUND: The community-based health insurance (CBHI) scheme is a growing initiative aimed at enhancing healthcare access for the most impoverished members of the community. The Ethiopian CBHI scheme aims to enhance access to essential healthcare services, including medical laboratory services, for the poorest members of the community, but there is limited evidence on satisfaction levels. The aim of this study was to assess the satisfaction level of CBHI beneficiaries with laboratory services and their associated factors among selected public hospitals in Jimma Zone, Oromia Region, Ethiopia. METHODS: A facility-based cross-sectional study was conducted on selected public hospitals in the Jimma Zone from September to October 2023. A total of 421 CBHI beneficiaries were enrolled in the study using a convenient sampling technique, and interviewers administered structured questionnaires to collect data. Data were entered into Epi-data and analyzed using the Statistical Package of Social Sciences version 25. Descriptive analysis was used to summarize independent variables; bivariate and multivariable logistic regression analyses were done to test the association between independent and dependent variables; and statistical significance was declared at P<0.05. RESULTS: More than half (55.8%) of the 419 study participants were female. Above half, 57.5% of the respondents were satisfied by the clinical laboratory services at public hospitals in Jimma Zone. Components with a higher satisfaction rate were providers' professional appearances (98.3%), procedures for specimen collection (87.6%), and availability of entertainment facilities at the waiting area (67.8%). On the contrary, longer waiting times to receive the test results (76.6%), inefficiency of the reception area (74.7%), and the inability of professionals to explain diagnostic procedures (58.0%) were associated with higher rates of dissatisfaction. Educational status and the number of hospital visits were found to have a statistically significant association with level of satisfaction with laboratory services. CONCLUSIONS: CBHI beneficiaries' satisfaction with laboratory service was at a moderate level in Jimma Zone public hospitals. Therefore, attention should be given to continuous monitoring of patients' satisfaction with services, improving reception areas, and practicing routine explanations about the purposes and procedures during specimen collection to improve the beneficiaries' satisfaction level with clinical laboratory services.

Effective Treatment of COVID-19 Infection with Repurposed Drugs: Case Reports.

The COVID-19 pandemic response has been hindered by the absence of an efficient antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The reason why the previous preventative approach to COVID-19 solely through vaccines has failed could be a lack of understanding of how quickly the SARS-CoV-2 virus evolves. Given the absence of specific treatments for the virus, efforts have been underway to explore treatment options. Drug repurposing involves identifying new therapeutic uses for approved drugs, proving to be a time-saving strategy with minimal risk of failure. In this study, we report the successful use of a multidrug approach in patients with COVID-19. Successful administration of multidrug therapy, such as combinations of hydroxychloroquine and azithromycin, doxycycline and ivermectin, or ivermectin, doxycycline, and azithromycin, has been reported. Multidrug therapy is effective because of the differing mechanisms of action of these drugs, and it may also mitigate the emergence of drug-resistant SARS-CoV-2 strains. The medicines were lopinavir/ritonavir (Kaletra), bamlanivimab (monoclonal antibody), glycopyrrolate-formoterol (Bevespi), ciclesonide (Alvesco), famotidine (Pepcid), and diphenhydramine (Benadryl).

Parental perceptions of an oral health promotion program in early childhood education and care settings: A qualitative study.

OBJECTIVES: Early Childhood Caries is a global health problem. The Bright Smiles Bright Futures (BSBF) program seeks to equip educators, children, and parents with skills and knowledge about oral health promotion habits early in life. The aim of this study was to examine parental perceptions of the BSBF program and identify key facilitators and barriers for its implementation. METHODS: Twelve mothers of children who participated in the BSBF program in five Early Childhood Education and Care (ECEC) settings in NSW, Australia were recruited in this qualitative study. Data were collected via focus groups and interviews, transcribed verbatim and coded to categorize for inductive thematic analysis. RESULTS: Five major themes emerged: Promoters of the BSBF oral health program, barriers to the BSBF oral health program implementation and participation, online resources, impact of the BSBF oral health program, and strategies for enhancing the BSBF oral health program. While participants reported that the program encouraged their children's toothbrushing, they found issues with the program's materials, ECEC center attendance, and communication about the oral health program with their children. The program improved message retention, attitudes, routines, and family perceptions toward oral health. Participants recommended oral health literacy, changed delivery formats, increased dental access, and inclusion of interactive elements to enhance the program. CONCLUSIONS: The findings from this study provide insight to improve parents' experiences and engagement in oral health promotion. This can help to raise awareness of the importance of child oral health among policymakers, healthcare professionals, and the public to inform public health policy discussions.

Evaluation of VITEK MS Version 3.0 MALDI-TOF for the identification of anaerobes, mycobacteria, Nocardia, and moulds.

PURPOSE: The identification of anaerobes, Mycobacterium and Nocardia species, and moulds by MALDI-TOF-MS remains a challenge. This study aimed to evaluate the performance of MALDI-TOF in the identification of these organisms. METHODS: A total of 382 strains, comprising 128 (33.5 %) anaerobes, 126(33.0 %) mycobacterial, 113(29.6 %), mycelial fungi, and 15(3.9 %) Nocardia species were evaluated by VITEK MS Version 3.0. The results were compared with the identification of the isolates by DNA sequence analysis. The DNA sequences used for analysis were the 16S rRNA for anaerobic bacteria, hsp65 gene for mycobacteria, whereas both 16S rRNA and hsp65 gene for Nocardia species, and internal transcribed spacer (ITS) and 28S rRNA gene's D1/D2 regions of fungi. RESULTS: The VITEK-MS accurately identified 78.3 % (299/382) of the strains at the species, and 9.4 % (36/382) at the genus level. Misidentifications were observed in 3.9 % (15/382) isolates. Of isolates tested, 8.4 % (32/382) were not identified by the system, and 7.06 % (27/382) were not included in the IVD database. CONCLUSION: An upgraded VITEK MS V3.0 database provides reasonably accurate and rapid identification of clinically relevant anaerobes, mycobacteria, Nocardia species, and moulds to the species level.

Trajectories of Sugar-Sweetened Beverage Intake in Early Life: Evidence from a Birth Cohort Study.

Infancy and early childhood are periods of dietary transition. Early exposure to specific foods and the establishment of dietary habits during this period can shape long-term food preferences and have lasting effects on health. This study aimed to examine the longitudinal trajectories of sugar-sweetened beverage (SSB) intake in Australian children from birth to age 3 years and identify early-life and socioeconomic factors influencing those trajectories. Mother-infant dyads (n = 934) from the Healthy Smiles Healthy Kids birth cohort study were interviewed on their weekly frequency of SSB intake at 4-month, 8-month, 1-year, 2-year, and 3-year age points. Group-based trajectory modelling analysis was performed to identify trajectories for SSB intake among Australian children. A multivariable logistic regression was performed to identify the maternal and child-related predictors of resulting trajectories. The intake of SSBs showed two distinct quadratic trajectories (high and low) with age. While the two trajectories remained distinctive throughout, the SSB consumption for both groups consistently increased between 4 months and 2 years of age and subsequently stabilised. Compared to low SSB consumers (75%), the high SSB consumers (25%) were significantly more likely to be living in households with three or more children (relative risk (RR): 1.59, 95%CI: 1.02-2.48), had low maternal education (left school < year 12-RR: 1.75, 95%CI: 1.09-2.81; completed year 12-RR: 1.57, 95%CI: 1.02-2.81), and resided in highly/the most socioeconomically disadvantaged areas (highly disadvantaged-RR: 1.89, 95%CI: 1.13-3.18; most disadvantaged-RR: 2.06, 95%CI: 1.25-3.38). Children's SSB intake patterns are established early in life as they transition from infancy to preschool age, and the trajectories of intake established during early childhood are strongly influenced by socioeconomic factors. Hence, interventions targeted to limit SSB intake and improve nutrition amongst children should occur in early life.

Local tumour control and patient survival after ruthenium-106 brachytherapy for small choroidal melanoma.

AIM: To report local tumour control, metastasis and survival rates of patients with small choroidal melanoma (CM) after treatment with ruthenium-106 (Ru-106) plaque brachytherapy. METHODS: Retrospective case series of 353 consecutive eyes with small CM (thickness ≤2.5 mm and largest basal diameter ≤16 mm) treated with Ru-106 brachytherapy at the London Ocular Oncology Service, between October 2004 and May 2019. RESULTS: The final cohort included 310 eyes and tumour recurrence was observed in 52 (17%) eyes. Ocular retention rate was 96%. Metastatic disease and tumour-related death occurred in 18 (5.8%) and 12 (3.9%) patients, respectively. Metastases were diagnosed after a median of 54 (54±35; range 3.6-118) months from initial treatment. Kaplan-Meier estimates for tumour recurrence, melanoma-related metastases and survival were 17% (95% CI 13.3% to 22.9%), 4.8% (95% CI 2.6% to 8.5%) and 98% (95% CI 94.4% to 99.1%) at 5 years and 26% (95% CI 18.3% to 35.3%), 16% (95% CI 8.7% to 27.7%) and 92% (95% CI 84.5% to 95.7%) at 10 years, respectively. On multivariable analysis, factors predictive for tumour recurrence included juxtapapillary location, larger plaque and final tumour thickness, and for metastasis exudative retinal detachment. CONCLUSION: Small CMs treated with Ru-106 brachytherapy show recurrence and death rates of 17% and 2% at 5 years and 26% and 8% at 10 years. As small CMs have better prognosis than large tumours, early treatment is the key for better survival outcomes.

Association of Breastfeeding and Early Childhood Caries: A Systematic Review and Meta-Analysis.

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.

Managing social-educational robotics for students with autism spectrum disorder through business model canvas and customer discovery.

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.

A Qualitative Study of Preschool Children's Perspectives on an Oral Health Promotion Program in New South Wales, Australia.

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.

Polymorphisms in Innate and Adaptive Immune Genes in Subjects with Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

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.

Whole genome sequencing for the prediction of resistant tuberculosis strains from northern India.

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.

Cholic Acid-Derived Gemini Amphiphile Can Eradicate Interkingdom Polymicrobial Biofilms and Wound Infections.

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.

Genetic QT Score and Sleep Apnea as Predictors of Sudden Cardiac Death in the UK Biobank.

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.

Genome-Wide Association Study of Gallstone Disease Identifies Novel Candidate Genomic Variants in a Latino Community of Southwest USA.

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.

Interventions to improve the nutritional status of children under 5 years in Ethiopia: a systematic review.

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).

Effectiveness of sensory adaptive dental environments to reduce psychophysiology responses of dental anxiety and support positive behaviours in children and young adults with intellectual and developmental disabilities: a systematic review and meta-analyses.

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).

The gene expression and proteomic profiling of Acanthamoeba isolates.

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.