Electronic Immunization Registry in Rwanda: Qualitative Study of Health Worker Experiences.

BACKGROUND: Monitoring childhood immunization programs is essential for health systems. Despite the introduction of an electronic immunization registry called e-Tracker in Rwanda, challenges such as lacking population denominators persist, leading to implausible reports of coverage rates of more than 100%. OBJECTIVE: This study aimed to assess the extent to which the immunization e-Tracker responds to stakeholders' needs and identify key areas for improvement. METHODS: In-depth interviews were conducted with all levels of e-Tracker users including immunization nurses, data managers, and supervisors from health facilities in 5 districts of Rwanda. We used an interview guide based on the constructs of the Human, Organization, and Technology-Fit (HOT-Fit) framework, and we analyzed and summarized our findings using the framework. RESULTS: Immunization nurses reported using the e-Tracker as a secondary data entry tool in addition to paper-based forms, which resulted in considerable dissatisfaction among nurses. While users acknowledged the potential of a digital tool compared to paper-based systems, they also reported the need for improvement of functionalities to support their work, such as digital client appointment lists, lists of defaulters, search and register functions, automated monthly reports, and linkages to birth notifications and the national identity system. CONCLUSIONS: Reducing dual documentation for users can improve e-Tracker use and user satisfaction. Our findings can help identify additional digital health interventions to support and strengthen the health information system for the immunization program.

Evaluation of contrast sensitivity in visually impaired individuals using K-CS test. A novel smartphone-based contrast sensitivity test-Design and validation.

BACKGROUND: To describe the development and investigate the accuracy of a novel smartphone-based Contrast Sensitivity (CS) application, the K-CS test. METHODS: A total of 67 visually impaired and 50 normal participants were examined monocularly using the novel digital K-CS test and the Pelli-Robson (PR) chart. The K-CS test examines letter contrast sensitivity in logarithmic units, using eight levels of contrast from logCS = ~0,1 to logCS = ~2,1 at two spatial frequencies of 1.5 and 3 cycles per degree (cpd). The K-CS test was compared to the gold standard, PR test and intra-session test repeatability was also examined. RESULTS: The K-CS test in normally sighted was found to agree well with the PR, providing comparable mean scores in logCS (±SD) (K-CS = 1.908 ± 0.06 versus PR = 1.93 ± 0.05) at 1.5 cpd and mean (± SD) logCS at 3 cpd (K-CS = 1.83 ± 0.13 versus PR = 1.86 ± 0.07). The mean best corrected visual acuity of visually impaired participants was 0.67 LogMAR (SD = 0.21) and the K-CS was also found to agree well with the Pelli-Robson in this group, with an equivalent mean (±SD) logCS at 1.5 cpd: (K-CS = 1.19 ± 0.27, PR = 1.15 ± 0.31), 3 cpd: K-CS = 1.01 ± 0.33, PR = 0.94 ± 0.34. Regarding the intra-session test repeatability, both the K-CS test and the PR test showed good repeatability in terms of the 95% limits of agreement (LoA): K-CS = ±0.112 at 1.5 cpd and ±0.133 at 3 cpd, PR = ±0.143 at 1.5 cpd and ±0.183 in 3 cpd in visually impaired individuals. CONCLUSION: The K-CS test provides a quick assessment of the CS both in normally sighted and visually impaired individuals. The K-CS could serve as an alternative tool to assess contrast sensitivity function using a smartphone and provides results that agree well with the commonly used PR test.

Mediators of parental educational differences in the intake of carbonated sugar-sweetened soft drinks among adolescents, and the moderating role of neighbourhood income.

BACKGROUND: Existing evidence suggests that the intake of sugar-sweetened beverages (SSB) among adolescents remains a public health concern and that socioeconomic differences in intake exist. Tackling these challenges requires identifying the factors associated with SSB intake and the mediators of socioeconomic differences in SSB intake among adolescents. Thus, this study aimed to explore (i) factors at different levels of the ecological model associated with the intake of carbonated soft drinks with added sugar (hereafter called soft drinks), (ii) mediators of the association between parental education and the intake of soft drinks(iii) whether neighbourhood income moderates the indirect effect of parental education on adolescents' soft drink intake through potential mediators. METHODS: Data from 826 7th graders in Oslo, Norway, who participated in the TACKLE cross-sectional study conducted in 2020 were used. The association between factors at the individual, interpersonal and neighbourhood food environment levels and the intake of soft drinks among adolescents was assessed, as well as the mediating roles of these factors for the differences in intake by parental education, using multiple logistic regression and mediation analysis, respectively. Moderated mediation analyses were used to explore whether an indirect effect of parental education on adolescents' soft drink intake through potential mediators varies across neighbourhood income areas. RESULTS: Higher perceived accessibility of SSB at home, increased parental modelling for SSB intake, and increased frequency of food/drink purchased from the neighbourhood store were associated with a higher intake of soft drinks among adolescents and mediated the differences in intake by parental education. Neighbourhood food environment factors were neither statistically significantly associated with adolescents' higher intake of soft drinks nor explained the differences in intake by parental education. Moderated mediation analysis showed that the mediating effect of perceived accessibility of SSB at home on the association between parental education and adolescent soft drink intake was stronger among those living in low neighbourhood income. CONCLUSIONS: Our study identified modifiable factors at the intrapersonal level (perceived accessibility of SSB at home and frequency of food/drink purchased from neighbourhood shops) and interpersonal levels (parental modelling for SSB intake) associated with a higher intake of soft drinks among adolescents and mediated the differences in the intake by parental education. The modifiable factors identified in this study could be targeted in public health initiatives among adolescents aimed at reducing the intake of soft drinks and the related differences by parental education.

Lay health workers in primary and community health care for maternal and child health: identification and treatment of wasting in children.

BACKGROUND: Since the early 2010s, there has been a push to enhance the capacity to effectively treat wasting in children through community-based service delivery models and thus reduce morbidity and mortality. OBJECTIVES: To assess the effectiveness of identification and treatment of moderate and severe wasting in children aged five years or under by lay health workers working in the community compared with health providers working in health facilities. SEARCH METHODS: We searched MEDLINE, CENTRAL, two other databases, and two ongoing trials registers to 24 September 2021. We also screened the reference lists of related systematic reviews and all included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised studies in children aged five years or under with moderate wasting (defined as weight-for-height Z-score (WHZ) below -2 but no lower than ≥ -3, or mid-upper-arm circumference (MUAC) below 125 mm but no lower than 115 mm, and no nutritional oedema) or severe wasting (WHZ below -3 or MUAC below 115 mm or nutritional oedema). Eligible interventions were: • identification by lay health workers (LHWs) of children with wasting (intervention 1); • identification by LHWs of children with wasting and medical complications needing referral (intervention 2); and • identification by LHWs of children with wasting without medical complications needing referral (intervention 3). Eligible comparators were: • identification and treatment of wasting by health professionals such as nurses or doctors (at health facilities); and • identification and treatment of wasting by health facility-based teams, including health professionals and LHWs. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials, extracted data and assessed risk of bias using the Cochrane risk of bias tool (RoB 2) and Cochrane Effective Practice and Organisation of Care (EPOC) guidelines. We used a random-effects model to meta-analyse data, producing risk ratios (RRs) for dichotomous outcomes in trials with individual allocation, adjusted RRs for dichotomous outcomes in trials with cluster allocation (using the generic inverse variance method in Review Manager 5), and mean differences (MDs) for continuous outcomes. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included two RCTs and five non-RCTs. Six studies were from African countries, and one was from Pakistan. Six studies included children with severe wasting, and one included children with moderate wasting. All studies offered home-based ready-to-use therapeutic food treatment and monitoring. Children received antibiotics in three studies, vitamins or micronutrients in three studies, and deworming treatment in two studies. In three studies, the comparison arm involved LHWs screening children for malnutrition and referring them to health facilities for diagnosis and treatment. All the non-randomised studies had a high overall risk of bias. Interventions 1 and 2 Identification and referral for treatment by LHWs, compared with treatment by health professionals following self-referral, may result in little or no difference in the percentage of children who recover from moderate or severe wasting (MD 1.00%, 95% confidence interval (CI) -2.53 to 4.53; 1 RCT, 29,475 households; low certainty). Intervention 3 Compared with treatment by health professionals following identification by LHWs, identification and treatment of severe wasting in children by LHWs: • may slightly reduce improvement from severe wasting (RR 0.93, 95% CI 0.86 to 0.99; 1 RCT, 789 participants; low certainty); • may slightly increase non-response to treatment (RR 1.44, 95% CI 1.04 to 2.01; 1 RCT, 789 participants; low certainty); • may result in little or no difference in the number of children with WHZ above -2 on discharge (RR 0.94, 95% CI 0.28 to 3.18; 1 RCT, 789 participants; low certainty); • probably results in little or no difference in the number of children with WHZ between -3 and -2 on discharge (RR 1.09, 95% CI 0.87 to 1.36; 1 RCT, 789 participants; moderate certainty); • probably results in little or no difference in the number of children with WHZ below -3 (severe wasting) on discharge (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT, 789 participants; moderate certainty); • probably results in little or no difference in the number of children with MUAC equal to or greater than 115 mm on discharge (RR 0.99, 95% CI 0.93 to 1.06; 1 RCT, 789 participants; moderate certainty); • results in little or no difference in weight gain per day (mean weight gain 0.50 g/kg/day higher, 95% CI 1.74 lower to 2.74 higher; 1 RCT, 571 participants; high certainty); • probably has little or no effect on relapse of severe wasting (RR 1.03, 95% CI 0.69 to 1.54; 1 RCT, 649 participants; moderate certainty); • may have little or no effect on mortality among children with severe wasting (RR 0.46, 95% CI 0.04 to 5.98; 1 RCT, 829 participants; low certainty); • probably has little or no effect on the transfer of children with severe wasting to inpatient care (RR 3.71, 95% CI 0.36 to 38.23; 1 RCT, 829 participants; moderate certainty); and • probably has little or no effect on the default of children with severe wasting (RR 1.48, 95% CI 0.65 to 3.40; 1 RCT, 829 participants; moderate certainty). The evidence was very uncertain for total MUAC gain, MUAC gain per day, total weight gain, treatment coverage, and transfer to another LHW site or health facility. No studies examined sustained recovery, deterioration to severe wasting, appropriate identification of children with wasting or oedema, appropriate referral of children with moderate or severe wasting, adherence, or adverse effects and other harms. AUTHORS' CONCLUSIONS: Identification and treatment of severe wasting in children who do not require inpatient care by LHWs, compared with treatment by health professionals, may lead to similar or slightly poorer outcomes. We found only two RCTs, and the evidence from non-randomised studies was of very low certainty for all outcomes due to serious risks of bias and imprecision. No studies included children aged under 6 months. Future studies must address these methodological issues.

Maternal vitamin D status and risk of childhood overweight at 5 years of age in two Nordic cohort studies.

Introduction: Maternal vitamin D status during pregnancy has been suggested to have a role in childhood adiposity development, but results are conflicting. Our aims were to investigate [1] the relationships between maternal 25-hydroxyvitamin D (25OHD) during pregnancy and the child's body mass index (BMI) and risk of overweight at 5 years of age, and [2] maternal pre-pregnancy BMI as effect modifier for these associations. Methods: Data sources included a subsample from the Norwegian Mother, Father and Child Cohort Study (MoBa sub-cohort; N = 2,744) and the Swedish GraviD cohort study (N = 891). Maternal 25OHD was analyzed in gestational week 18 in the MoBa sub-cohort and week 10 in the GraviD cohort. In the MoBa sub-cohort, parents reported their child's documented measures of weight and length or height from the health card at routine check-up. In the GraviD cohort, this information was collected directly from medical records. Childhood overweight (including obesity) was identified using the International Obesity Task Force cut-offs. Linear and logistic regression models were used to investigate the association between maternal 25OHD and child's BMI and risk of overweight at 5 years of age in each cohort separately, and in a pooled dataset. Results: In the pooled analysis, maternal 25OHD <30 nmol/L was associated with lower BMI in children at 5 years of age, but not with risk of overweight. Interaction analysis showed that the association was predominant among children of mothers with pre-pregnancy BMI ≥25 kg/m2. Conclusion: Low maternal vitamin D status, particularly in mothers with overweight or obesity, predicted lower BMI in their five-year-old children. However, there was no evidence of an effect on overweight in these children.

Vitamin D intake and determinants of vitamin D status during pregnancy in The Norwegian Mother, Father and Child Cohort Study.

Background: Norwegian data on vitamin D status among pregnant women indicate a moderate to high prevalence of insufficient vitamin D status (25-hydroxyvitamin D (25OHD) concentrations ≤50 nmol/L). There is a lack of population-based research on vitamin D intake and determinants of 25OHD in pregnant women from northern latitudes. The aims of this study were (1) to evaluate total vitamin D intake from both diet and supplements, (2) to investigate determinants of vitamin D status, and (3) to investigate the predicted response in vitamin D status by total vitamin D intake, in pregnant Norwegian women. Methods: In total, 2,960 pregnant women from The Norwegian Environmental Biobank, a sub-study within The Norwegian Mother, Father and Child Cohort Study (MoBa), were included. Total vitamin D intake was estimated from a food frequency questionnaire in gestational week 22. Concentrations of plasma 25OHD was analyzed by automated chemiluminescent microparticle immunoassay method in gestational week 18. Candidate determinant variables of 25OHD were chosen using stepwise backward selection and investigated using multivariable linear regression. Predicted 25OHD by total vitamin D intake, overall and stratified by season and pre-pregnancy BMI, was explored using restricted cubic splines in an adjusted linear regression. Results: Overall, about 61% of the women had a total vitamin D intake below the recommended intake. The main contributors to total vitamin D intake were vitamin D supplements, fish, and fortified margarine. Higher 25OHD concentrations were associated with (in descending order of the beta estimates) summer season, use of solarium, higher vitamin D intake from supplements, origin from high income country, lower pre-pregnancy BMI, higher age, higher vitamin D intake from foods, no smoking during pregnancy, higher education and energy intake. During October-May, a vitamin D intake according to the recommended intake was predicted to reach sufficient 25OHD concentrations >50 nmoL/L. Conclusion: The findings from this study highlight the importance of the vitamin D intake, as one of few modifiable determinants, to reach sufficient 25OHD concentrations during months when dermal synthesis of vitamin D is absent.

Melanoma: BRAFi Rechallenge.

Melanoma is the most aggressive type of skin cancer. Half of melanoma cases are characterized by the mutation BRAF V600. The case presented concerns a 41-year-old patient with locally advanced melanoma, being positive in mutation BRAF V600. The patient underwent surgery and received additional targeted therapy as part of a clinical study. In subsequent disease progression, immunotherapy was used. When the disease progressed again while the patient was in a good performance status, targeted therapy was administered again, and a good response was noted, making the patient reach a statistically significant overall survival, exceeding four years. Targeted therapy has proven to be an important tool in the treatment of melanoma. The use of BRAFi targeted therapy does not exclude the option of readministration at subsequent disease progression (BRAFi rechallenge). Preclinical models suggest that the resistance mechanism of cancer cells to BRAFi therapy bends, as these cell clones lose their evolutionary advantage after stopping BRAFi. Cell clones sensitive to BRAFi may then outcompete, making the treatment effective again. Therapeutical dilemmas in the management of patients with locally advanced melanoma that progresses to metastatic cancer are discussed.

Gaucher Disease Type 2 Manifested as Hemophagocytic Lymphohistiocytosis in a Neonate in the COVID-19 Era.

BACKGROUND: A term neonate presented with persistent severe thrombocytopenia, elevated liver enzymes, conjugated hyperbilirubinemia, hepatosplenomegaly, and mild hypotonia. OBSERVATIONS: A thorough workup for infections, congenital thrombocytopenias, and neonatal malignancies was negative. Because of increased anti-SARS-CoV-2 IgG antibodies after maternal COVID-19, multisystem inflammatory syndrome of neonates was considered and intravenous immunoglobulin was administered. The clinical condition of the neonate deteriorated and due to laboratory evidence of hyperinflammation, hemophagocytic lymphohistiocytosis was suspected, and treatment with etoposide and dexamethasone was initiated with temporary stabilization. Gaucher disease type 2 was eventually diagnosed. CONCLUSION: Gaucher disease can rarely present in neonates as hemophagocytic lymphohistiocytosis.

Ultra-processed food consumption and associations with biomarkers of nutrition and inflammation in pregnancy: The Norwegian Environmental Biobank.

Background: A high consumption of ultra-processed foods (UPFs) is often associated with low nutritional quality, but data on associations with biomarkers are scarce. We aimed to explore associations between UPF intake, diet quality, and concentrations of biomarkers of nutrition and inflammation measured in mid-pregnancy. Methods: This cross-sectional study included n = 2,984 pregnant women recruited during 2002-2008 in the Norwegian Mother, Father, and Child Cohort Study (MoBa). Concentrations of C-reactive protein (CRP) and 21 nutritional biomarkers including carotenes (α-carotene, ß-carotene, γ-carotene, α-cryptoxanthin, ß-cryptoxanthin, lutein, lycopene), vitamins [α-tocopherol, γ-tocopherol, 25-hydroxyvitamin D (25-OH-D), retinol], creatinine, elements (K, Na, Co, Cu, Mn, Mo, Se, Zn), and ferritin (Fe) were measured in blood and urine collected in mid-pregnancy. Habitual diet in pregnancy was assessed using a validated semi-quantitative food frequency questionnaire. We calculated the relative (%) energy contribution of UPF to overall intake according to the NOVA classification. We also applied a diet quality index (DQI) adapted to assess adherence to Norwegian dietary guidelines (DQI; min-max: 0-110, higher score meaning higher adherence). We present summary statistics for biomarker concentrations and explored associations between UPF intake or the DQI and measured biomarkers using adjusted linear, logistic, and generalized additive regression models. Results: Ultra-processed food intake was positively associated with biomarker concentrations of vitamin E (γ-tocopherol), creatinine, K, and Na [ßs: 5.6 to 17% increase in biomarker concentration per interquartile range (IQR) increase in UPF intake] and negatively associated with carotenoids (α-carotene, ß-carotene, γ-carotene, α-cryptoxanthin, ß-cryptoxanthin, lutein, lycopene), vitamin A, Mo, and Se (ßs: -2.1 to -18%). Inversely, high diet quality (i.e., the DQI) was positively associated with concentrations of carotenoids, vitamins [vitamin A (retinol) and D (25-OH-D)], and Se (ß: 1.5 to 25%) and negatively associated with vitamin E (γ-tocopherol), creatinine, and Na (ß: -4.8 to -8.3%). A weak, positive association was found between UPF and CRP (ß: 5.4%, 95% CI 0.12-11%). Conclusion: High UPF intake was associated with reduced concentrations of nutrition biomarkers in mid-pregnancy. Associations in the opposite direction were found with high adherence to the Norwegian dietary guidelines, suggesting that the two dietary scoring systems capture diet quality in a mirrored manner in this population.

Multi-omics signatures of the human early life exposome.

Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1301 mother-child pairs, we associate individual exposomes consisting of >100 chemical, outdoor, social and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, proteins and metabolites) in childhood. We identify 1170 associations, 249 in pregnancy and 921 in childhood, which reveal potential biological responses and sources of exposure. Pregnancy exposures, including maternal smoking, cadmium and molybdenum, are predominantly associated with child DNA methylation changes. In contrast, childhood exposures are associated with features across all omics layers, most frequently the serum metabolome, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions, among others. Our comprehensive and unique resource of all associations ( https://helixomics.isglobal.org/ ) will serve to guide future investigation into the biological imprints of the early life exposome.

Dietary Intake Contributed the Most to Chlorinated Paraffin Body Burden in a Norwegian Cohort.

Determining the major human exposure pathways is a prerequisite for the development of effective management strategies for environmental pollutants such as chlorinated paraffins (CPs). As a first step, the internal and external exposure to CPs were quantified for a well-defined human cohort. CPs in participants' plasma and diet samples were analyzed in the present study, and previous results on paired air, dust, and hand wipe samples were used for the total exposure assessment. Both one compartment pharmacokinetic modeling and forensic fingerprinting indicate that dietary intake contributed the most to body burden of CPs in this cohort, contributing a median of 60-88% of the total daily intakes. The contribution from dust ingestion and dermal exposure was greater for the intake of long-chain CPs (LCCPs) than short-chain CPs (SCCPs), while the contribution from inhalation was greater for the intake of SCCPs than medium-chain CPs (MCCPs) and LCCPs. Significantly higher concentrations of SCCPs and MCCPs were observed in diets containing butter and eggs, respectively (p < 0.05). Additionally, other exposure sources were correlated to plasma levels of CPs, including residence construction parameters such as the construction year (p < 0.05). This human exposure to CPs is not a local case. From a global perspective, there are major knowledge gaps in biomonitoring and exposure data for CPs from regions other than China and European countries.

Maternal vitamin D status in relation to infant BMI growth trajectories up to 2 years of age in two prospective pregnancy cohorts.

Background: Early childhood growth can affect the child's health status later in life. Maternal vitamin D status has been suggested to affect early childhood growth. However, there is a lack of studies investigating the role of maternal vitamin D status on growth trajectories during infancy. By using growth mixture modeling (GMM), maternal vitamin D status during pregnancy can be investigated in relation to different classes of infant growth trajectories. Objectives: To examine the association between maternal 25-hydroxyvitamin D (25OHD) and classes of infant body mass index (BMI) growth trajectories. Methods: Mother-child pairs were included from the Norwegian Mother, Father, and Child Cohort Study (MoBa, n = 2522) and the Swedish GraviD cohort (n = 862). Maternal 25OHD in pregnancy was analyzed by liquid chromatography tandem mass spectrometry. Children's weights and heights were registry-based. GMM identified classes of infant BMI growth trajectories up to 2 years. The association between maternal 25OHD and infant BMI class by cohort was estimated using a log-link generalized linear model. Mixed model analysis estimated the pooled association including both cohorts. Results: Two infant BMI classes were identified, stable normal and stable high. In MoBa, maternal 25OHD <50 and 50-75 nmol/L were associated (RR 2.70, 95% CI 1.26-5.77 and RR 2.56, 95% CI 1.20-5.47) with a higher risk of the infant stable high BMI class, compared with 25OHD >75 nmol/L. In GraviD, no association was found. In pooled analysis, maternal 25OHD ≤75 nmol/L was non-significantly associated with a higher risk of the stable high BMI growth class. Conclusions: Maternal 25OHD ≤75 nmol/L may be associated with a higher class of BMI growth trajectory during infancy.

Design and Validation of a New Smartphone-Based Reading Speed App (GDRS-Test) for the Greek Speaking Population.

Purpose: To present a novel smartphone-based application (GDRS-test, Greek Digital Reading Speed - test) for the assessment of reading speed, to evaluate, whether this test could be easily and reliably used by patients with visual impairment and normal individuals serving as an adjunctive tool for their visual examination. Patients and Methods: One hundred and five visually impaired and 32 normal eyes were examined. Depending on existing active ocular pathology, patients were divided into a non-macular and a macular group, We examined the reading performance for continuous text (MNREAD chart) and random unrelated words of the new smartphone-based reading speed app, monocularly. The patients' best-corrected visual acuity ranged from 1.3 to 0.2 logMAR. Examinees were asked to read aloud (at a 40 cm distance) a series of 30 random two-syllable and then 30 three-syllable Greek words, without semantic connection. Reading speed was measured as correct words per minute for critical print size. The individuals were examined twice within 2 weeks for test-retest reliability. Correlations and comparisons concerning each group adjusted for age and visual acuity were performed. Results: There was moderate correlation between MNREAD and 2SYL SPEED (Reading speed for 2-syllable) (Pearson's rho = 0.589, p < 0.001) and 3SYL SPEED (Reading speed for 3-syllable) (Pearson's rho = 0.617, p < 0.001) for healthy individuals. The mean 2SYL SPEED and 3SYL SPEED for Individuals of the maculopathies group or non-maculopathies group were significantly lower compared to normal individuals adjusted for age and visual acuity [B (95% CI): -93.077 (-104.165, -81.98), p < 0.001] and [B (95% CI): -92.254 (-104.196, -80.312), p < 0.001], respectively. The test-retest analysis showed a good agreement for patients and healthy individuals. Conclusion: The novel-reading speed application for the Greek-speaking population was found to accurately detect differences between patients with visual impairment and healthy individuals. It was designed and constructed with the intention to ease and improve the ophthalmic examination allowing individuals to self-evaluate reading speed by transmitting the result to their physician.

Association of Prenatal Exposure to Endocrine-Disrupting Chemicals With Liver Injury in Children.

Importance: Prenatal exposures to endocrine-disrupting chemicals (EDCs) may increase the risk for liver injury in children; however, human evidence is scarce, and previous studies have not considered potential EDC-mixture effects. Furthermore, the association between prenatal EDC exposure and hepatocellular apoptosis in children has not been studied previously. Objective: To investigate associations of prenatal exposure to EDC mixtures with liver injury risk and hepatocellular apoptosis in childhood. Design, Setting, and Participants: This prospective cohort study used data collected from April 1, 2003, to February 26, 2016, from mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort studies from 6 European countries (France, Greece, Lithuania, Norway, Spain, and the UK). Data were analyzed from April 1, 2021, to January 31, 2022. Exposures: Three organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 3 phenols, 4 parabens, 10 phthalates, 4 organophosphate pesticides, 5 perfluoroalkyl substances, and 9 metals. Main Outcomes and Measures: Child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and CK-18 were measured at 6 to 11 years of age. Risk for liver injury was defined as having ALT, AST, and/or GGT levels above the 90th percentile. Associations of liver injury or cytokeratin 18 (CK-18) levels with each chemical group among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy were estimated using 2 complimentary exposure-mixture methods: bayesian weighted quantile sum (BWQS) and bayesian kernel machine regression. Results: The study included 1108 mothers (mean [SD] age at birth, 31.0 [4.7] years) and their singleton children (mean [SD] age at liver assessment, 8.2 [1.6] years; 598 [54.0%] boys). Results of the BWQS method indicated increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (odds ratio [OR], 1.44 [95% credible interval (CrI), 1.21-1.71]), PBDEs (OR, 1.57 [95% CrI, 1.34-1.84]), perfluoroalkyl substances (OR, 1.73 [95% CrI, 1.45-2.09]), and metals (OR, 2.21 [95% CrI, 1.65-3.02]). Decreased odds of liver injury were associated with high-molecular-weight phthalates (OR, 0.74 [95% CrI, 0.60-0.91]) and phenols (OR, 0.66 [95% CrI, 0.54-0.78]). Higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (ß, 5.84 [95% CrI, 1.69-10.08] IU/L) and PBDEs (ß, 6.46 [95% CrI, 3.09-9.92] IU/L). Bayesian kernel machine regression showed associations in a similar direction as BWQS for all EDCs and a nonlinear association between phenols and CK-18 levels. Conclusions and Relevance: With a combination of 2 state-of-the-art exposure-mixture approaches, consistent evidence suggests that prenatal exposures to EDCs are associated with higher risk for liver injury and CK-18 levels and constitute a potential risk factor for pediatric nonalcoholic fatty liver disease.

Lipoprotein profiles associated with exposure to poly- and perfluoroalkyl substances (PFASs) in the EuroMix human biomonitoring study.

Exposure to per- and polyfluoroalkyl substances (PFASs) is associated with increased blood cholesterol. Although elevated cholesterol is a well-established risk factor for cardiovascular diseases (CVD), it is not clear whether PFASs affect this risk. Lipoprotein subclasses are emerging biomarkers for disease risk and lipoprotein profiling may provide an insight to physiological implications of PFAS exposure. We explored the association between serum PFAS concentrations and lipoprotein subclasses in a cross-sectional study. We determined the concentrations and lipid composition of the major subclasses of lipoproteins in plasma samples from 127 adult participants of the EuroMix human biomonitoring study by nuclear magnetic resonance (NMR). Serum concentrations of 17 PFASs showed a detection frequency between 30 and 100% and were included in further analyses. We examined the associations between PFAS concentrations and lipoprotein subclasses by linear mixed-effect regression models, adjusted for confounders. In the adjusted models, positive associations were found between several PFASs and cholesterol concentrations in large to medium sized HDL and medium sized LDL particles. We found a 4-12% increase in HDL cholesterol per interquartile range (IQR) increase for several PFASs. In women the associations with PFNA, PFUnDA, PFDoDA and PFOS were significant after adjustment for multiple comparisons. Similar magnitude of change was observed between longer chained PFASs and LDL cholesterol, and a few of these associations reached significance for cholesterol in large to medium LDL particle sizes in women. No significant associations with plasma triglycerides were observed. However, most PFASs tended to be associated with reduction in VLDL (very low-density lipoproteins) particle number and VLDL triglyceride. Findings from this exploratory study, suggest that background PFAS exposures influence particle size distributions and lipid composition of plasma lipoprotein subclasses, and that these effects may be more prominent in women. A two-points lipoprofiling for all subjects indicated both low intra-individual variability and good analytical reproducibility.

Design of a novel smartphone-based photostress recovery time test for detecting abnormalities in the macula. A cross-sectional study.

Background: The study aims to present a new smartphone-based photostress recovery time test (K-PSRT test) that measures the stimulus-specific loss of visual sensitivity, as well as the differentiation between normal from abnormal macular function. This novel test defines a new standardized photostress application as an alternative tool for incorporation into clinical practice. Materials and methods: A total of 48 visually impaired eyes and 47 normal sighted age-matched controls eyes were enrolled in the study. The median age in subjects with impairment was 71.0 years, while the median age in normal subjects was 70.0 years. A light produced by the smartphone camera at approximately 5 cm distance, perpendicular to the eye up 10 s filled the pupil. The photostress recovery time was assessed immediately after the exposure by asking the subjects to read correctly at least three successive letters of size corresponding to the previous line of the BCVA line at a distance of 40 cm. The digital photostress testing was performed with the best-corrected visual acuity (BCVA). The patients were examined twice within 2 weeks. Correlations among the recovery times, the visual acuity, and the contrast sensitivity function as well as correlations concerning each specific ocular disease were also performed. Furthermore, correlations among technology, usability, and ease of performance in both groups were analyzed. Results: The initial median photostress recovery time in patients with impaired eyes was 83.5 (68.5, 126.0), while in the normal individuals was 39.0 (14.0, 43.0). The median visual acuity in individuals with impairment was 0.59 logMAR (0.40, 0.90), whereas in the normal individuals was -0,06 logMAR. Test-retest reliability study was performed on 26 eyes (16 males, 10 females) for visually impaired eyes as well as on 35 normal eyes (19 males, 16 females). Concerning the reliability, the average Intraclass Correlation Coefficients (with 95% confidence intervals) ICC (95% CI) = 0,99 (0,98-1,00), indicating significant correlation between them (p < 0.01). The coefficient of repeatability for eye measurements reaches clinically acceptable levels, which is demonstrated with increased repeatability and consistency. The recovery time in patients with diabetic retinopathy was statistically significantly lower than in those with dry age-related macular degeneration (p = 0.027) and those with wet age-related macular degeneration (p = 0.032). The patient group has lower scores concerning technology, usability, and ease of performance compared to the normal. Conclusions: This new testing modality (K-Photostress Recovery time test), is designed to be an easily implemented measurement in ophthalmic practice, and it can expand our understanding of macular function. The above findings support the usefulness of a novel reproducible photostress application as an indicator of macular pathology.

Mediators of differences by parental education in weight-related outcomes in childhood and adolescence in Norway.

Studies exploring mediators of socioeconomic inequalities in excess weight gain in early-life and subsequent overweight/obesity (OW/OB) among youth are limited. Thus, this study examined the mediating role of prenatal and early postnatal factors and child energy balance-related behaviours (EBRB) in the effects of parental education on (i) excess weight gain from birth to 2 years and (ii) OW/OB at 5, 8 and 14 years. The Norwegian Mother, Father and Child Cohort Study was used to include participants at the ages of 2 (n = 59,597), 5 (n = 27,134), 8 (n = 28,285) and 14 (n = 11,278) years. Causal mediation analyses using the inverse odds weighting approach were conducted. Children of low-educated parents had a higher conditional excess weight gain at 2 years compared to children of high-educated parents (total effect, RRTE = 1.06; 95% CI 1.01, 1.10). The joint mediation effects of the prenatal and early postnatal factors explained most of the total effect of low education on conditional excess weight gain at 2 years. Children of low-educated parents had a higher risk of OW/OB at 5, 8 and 14 years compared to children of high-educated parents. The mediators jointly explained 63.7%, 67% and 88.9% of the total effect of parental education on OW/OB among 5, 8 and 14 year-old-children, respectively. Of the total mediated effects at 5, 8 and 14 years, the prenatal and early postnatal mediators explained 59.2%, 61.7% and 73.7%, whereas the child EBRB explained 10.3%, 15.8.0%% and 34.8%. The mediators included were found to have a considerable mediating effect in the associations explored, in particular the prenatal and early postnatal factors. If truly causal, the findings could indicate potential targets for interventions to tackle socioeconomic inequalities in OW/OB from birth to adolescence.

Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health.

Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used 1H NMR spectroscopy in a multicountry study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate, N-methylnicotinic acid, urea, and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food consumption and also had higher capacity in discriminating children's diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease.

Diet quality of Norwegian children at 3 and 7 years: changes, predictors and longitudinal association with weight.

BACKGROUND/OBJECTIVES: Poor diet quality in early life can have long-term health effects, but the evidence is largely from cross-sectional studies. Our objective was to examine diet quality of Norwegian children by applying a-priori diet quality indices, identify early life determinants and examine prospective associations with overweight. SUBJECTS/METHODS: We included 34,074 preschoolers (3-year-olds) and 18,350 school-aged children (7-years-olds) from the prospective, population-based Norwegian Mother, Father and Child Cohort Study. Diet quality was assessed as (i) adherence to a Mediterranean diet, estimated by the food frequency-based Mediterranean Diet Score (fMDS, score range: 0-6) and (ii) by the diet quality index (DQI, score range: -33% to 100%), reflecting compliance to food-based dietary guidelines. In multivariate analyses we explored perinatal and childhood characteristics as potential determinants of diet quality. We used logistic regression to examine the associations between diet quality at 3 years and BMI status at 8 years, adjusting for relevant confounders and diet quality at 7 years. RESULTS: One in three children had high MD adherence at 3 and 8 years, and DQI (mean 60%) at 3 and 7 years was strongly correlated (r = 0.48, p < 0.001). Short breastfeeding duration, physical activity and sleep duration and long screentime at 18 months were associated with 2-3% lower DQI at 3 years. At both ages, maternal diet quality was the strongest prospective predictor of DQI (beta = 5%, 95% CI = 4.7, 5.2 and beta = 3.1%, 95% CI = 2.8, 3.4), and screentime was the strongest cross-sectional predictor (beta = -5.2%, 95% CI = -5.9, -4.5 and beta = -4.1%, 95% CI = -5.0, -3.2). High DQI score at 3 years, but not MD adherence, was associated with a lower risk for overweight (including obesity) at 8 years, compared to low DQI (lower tertile) (adjusted OR = 0.77, 95% CI = 0.62, 0.96). CONCLUSIONS: Our study provides evidences that high diet quality in early childhood may reduce the risk for overweight in later childhood, independent of the current dietary behaviors.